5vjh › Citations

Ratchet-like polypeptide translocation mechanism of the AAA+ disaggregase Hsp104.

Gates SN, Yokom AL, Lin J, Jackrel ME, Rizo AN, Kendsersky NM, Buell CE, Sweeny EA, Mack KL, Chuang E, Torrente MP, Su M, Shorter J, Southworth DR
Science 357 273-279 (2017)
Related entries: 5vy8, 5vy9, 5vya

Cited: 157 times
EuropePMC logo PMID: 28619716

Abstract

Hsp100 polypeptide translocases are conserved members of the AAA+ family (adenosine triphosphatases associated with diverse cellular activities) that maintain proteostasis by unfolding aberrant and toxic proteins for refolding or proteolytic degradation. The Hsp104 disaggregase from Saccharomyces cerevisiae solubilizes stress-induced amorphous aggregates and amyloids. The structural basis for substrate recognition and translocation is unknown. Using a model substrate (casein), we report cryo-electron microscopy structures at near-atomic resolution of Hsp104 in different translocation states. Substrate interactions are mediated by conserved, pore-loop tyrosines that contact an 80-angstrom-long unfolded polypeptide along the axial channel. Two protomers undergo a ratchet-like conformational change that advances pore loop-substrate interactions by two amino acids. These changes are coupled to activation of specific nucleotide hydrolysis sites and, when transmitted around the hexamer, reveal a processive rotary translocation mechanism and substrate-responsive flexibility during Hsp104-catalyzed disaggregation.

Reviews - 5vjh mentioned but not cited (6)

  1. (Dis)Solving the problem of aberrant protein states. Fare CM, Shorter J. Dis Model Mech 14 dmm048983 (2021)
  2. Stairway to translocation: AAA+ motor structures reveal the mechanisms of ATP-dependent substrate translocation. Gates SN, Martin A. Protein Sci 29 407-419 (2020)
  3. The Cryo-EM Effect: Structural Biology of Neurodegenerative Disease Proteostasis Factors. Creekmore BC, Chang YW, Lee EB. J Neuropathol Exp Neurol 80 494-513 (2021)
  4. A History of Molecular Chaperone Structures in the Protein Data Bank. Bascos NAD, Landry SJ. Int J Mol Sci 20 (2019)
  5. A conserved strategy for structure change and energy transduction in Hsp104 and other AAA+ protein motors. Ye X, Mayne L, Englander SW. J Biol Chem 297 101066 (2021)
  6. Molecular mechanisms of amyloid disaggregation. Low KJY, Venkatraman A, Mehta JS, Pervushin K. J Adv Res 36 113-132 (2022)

Articles - 5vjh mentioned but not cited (9)

  1. Ratchet-like polypeptide translocation mechanism of the AAA+ disaggregase Hsp104. Gates SN, Yokom AL, Lin J, Jackrel ME, Rizo AN, Kendsersky NM, Buell CE, Sweeny EA, Mack KL, Chuang E, Torrente MP, Su M, Shorter J, Southworth DR. Science 357 273-279 (2017)
  2. The AAA ATPase Vps4 binds ESCRT-III substrates through a repeating array of dipeptide-binding pockets. Han H, Monroe N, Sundquist WI, Shen PS, Hill CP. Elife 6 (2017)
  3. Structure of Calcarisporiella thermophila Hsp104 Disaggregase that Antagonizes Diverse Proteotoxic Misfolding Events. Michalska K, Zhang K, March ZM, Hatzos-Skintges C, Pintilie G, Bigelow L, Castellano LM, Miles LJ, Jackrel ME, Chuang E, Jedrzejczak R, Shorter J, Chiu W, Joachimiak A. Structure 27 449-463.e7 (2019)
  4. ATP hydrolysis-coupled peptide translocation mechanism of Mycobacterium tuberculosis ClpB. Yu H, Lupoli TJ, Kovach A, Meng X, Zhao G, Nathan CF, Li H. Proc. Natl. Acad. Sci. U.S.A. 115 E9560-E9569 (2018)
  5. Conformational plasticity of the ClpAP AAA+ protease couples protein unfolding and proteolysis. Lopez KE, Rizo AN, Tse E, Lin J, Scull NW, Thwin AC, Lucius AL, Shorter J, Southworth DR. Nat Struct Mol Biol 27 406-416 (2020)
  6. Structural and mechanistic insights into Hsp104 function revealed by synchrotron X-ray footprinting. Sweeny EA, Tariq A, Gurpinar E, Go MS, Sochor MA, Kan ZY, Mayne L, Englander SW, Shorter J. J Biol Chem 295 1517-1538 (2020)
  7. Hydrogen exchange reveals Hsp104 architecture, structural dynamics, and energetics in physiological solution. Ye X, Lin J, Mayne L, Shorter J, Englander SW. Proc. Natl. Acad. Sci. U.S.A. 116 7333-7342 (2019)
  8. Active conformation of the p97-p47 unfoldase complex. Xu Y, Han H, Cooney I, Guo Y, Moran NG, Zuniga NR, Price JC, Hill CP, Shen PS. Nat Commun 13 2640 (2022)
  9. Mining Disaggregase Sequence Space to Safely Counter TDP-43, FUS, and α-Synuclein Proteotoxicity. Tariq A, Lin J, Jackrel ME, Hesketh CD, Carman PJ, Mack KL, Weitzman R, Gambogi C, Hernandez Murillo OA, Sweeny EA, Gurpinar E, Yokom AL, Gates SN, Yee K, Sudesh S, Stillman J, Rizo AN, Southworth DR, Shorter J. Cell Rep 28 2080-2095.e6 (2019)


Reviews citing this publication (40)

  1. The molecular principles governing the activity and functional diversity of AAA+ proteins. Puchades C, Sandate CR, Lander GC. Nat Rev Mol Cell Biol 21 43-58 (2020)
  2. Structure and Function of the 26S Proteasome. Bard JAM, Goodall EA, Greene ER, Jonsson E, Dong KC, Martin A. Annu. Rev. Biochem. 87 697-724 (2018)
  3. Structure, Dynamics and Function of the 26S Proteasome. Mao Y. Subcell Biochem 96 1-151 (2021)
  4. Transport mechanisms at the malaria parasite-host cell interface. Beck JR, Ho CM. PLoS Pathog 17 e1009394 (2021)
  5. Microtubule dynamics: an interplay of biochemistry and mechanics. Brouhard GJ, Rice LM. Nat. Rev. Mol. Cell Biol. 19 451-463 (2018)
  6. Structures, Functions, and Dynamics of ESCRT-III/Vps4 Membrane Remodeling and Fission Complexes. McCullough J, Frost A, Sundquist WI. Annu. Rev. Cell Dev. Biol. 34 85-109 (2018)
  7. AAA+ Protein-Based Technologies to Counter Neurodegenerative Disease. March ZM, Mack KL, Shorter J. Biophys J 116 1380-1385 (2019)
  8. Illuminating how malaria parasites export proteins into host erythrocytes. Matthews KM, Pitman EL, de Koning-Ward TF. Cell Microbiol 21 e13009 (2019)
  9. Protein-Protein Interactions in the Molecular Chaperone Network. Freilich R, Arhar T, Abrams JL, Gestwicki JE. Acc. Chem. Res. 51 940-949 (2018)
  10. AAA+ ATPases: structural insertions under the magnifying glass. Jessop M, Felix J, Gutsche I. Curr Opin Struct Biol 66 119-128 (2021)
  11. Amyloid Fragmentation and Disaggregation in Yeast and Animals. Kushnirov VV, Dergalev AA, Alexandrov AI. Biomolecules 11 1884 (2021)
  12. The PDB and protein homeostasis: From chaperones to degradation and disaggregase machines. Saibil HR. J Biol Chem 296 100744 (2021)
  13. AAA+ proteins: one motor, multiple ways to work. Lin J, Shorter J, Lucius AL. Biochem Soc Trans 50 895-906 (2022)
  14. Come Together: Protein Assemblies, Aggregates and the Sarcostat at the Heart of Cardiac Myocyte Homeostasis. Islam M, Diwan A, Mani K. Front Physiol 11 586 (2020)
  15. Mechanisms for Curing Yeast Prions. Greene LE, Saba F, Silberman RE, Zhao X. Int J Mol Sci 21 E6536 (2020)
  16. Prion-Like Proteins in Phase Separation and Their Link to Disease. Sprunger ML, Jackrel ME. Biomolecules 11 1014 (2021)
  17. Protein Aggregation and Disaggregation in Cells and Development. Fassler JS, Skuodas S, Weeks DL, Phillips BT. J Mol Biol 433 167215 (2021)
  18. Resisting the Heat: Bacterial Disaggregases Rescue Cells From Devastating Protein Aggregation. Katikaridis P, Bohl V, Mogk A. Front Mol Biosci 8 681439 (2021)
  19. Spiraling in Control: Structures and Mechanisms of the Hsp104 Disaggregase. Shorter J, Southworth DR. Cold Spring Harb Perspect Biol 11 (2019)
  20. Amyloid assembly and disassembly. Chuang E, Hori AM, Hesketh CD, Shorter J. J. Cell. Sci. 131 (2018)
  21. Comparative Analysis of the Structure and Function of AAA+ Motors ClpA, ClpB, and Hsp104: Common Threads and Disparate Functions. Duran EC, Weaver CL, Lucius AL. Front Mol Biosci 4 54 (2017)
  22. Impact of Amyloid Polymorphism on Prion-Chaperone Interactions in Yeast. Killian AN, Miller SC, Hines JK. Viruses 11 (2019)
  23. Recent Insights into the Structure and Function of Mycobacterial Membrane Proteins Facilitated by Cryo-EM. Bendre AD, Peters PJ, Kumar J. J Membr Biol 254 321-341 (2021)
  24. Structural features underlying recognition and translocation of extracellular polysaccharides. Zimmer J. Interface Focus 9 20180060 (2019)
  25. Structure and mechanism of the ESCRT pathway AAA+ ATPase Vps4. Han H, Hill CP. Biochem. Soc. Trans. 47 37-45 (2019)
  26. AAA+ ATPases in Protein Degradation: Structures, Functions and Mechanisms. Zhang S, Mao Y. Biomolecules 10 (2020)
  27. Crossing the Vacuolar Rubicon: Structural Insights into Effector Protein Trafficking in Apicomplexan Parasites. Egea PF. Microorganisms 8 (2020)
  28. Differential Interactions of Molecular Chaperones and Yeast Prions. Barbitoff YA, Matveenko AG, Zhouravleva GA. J Fungi (Basel) 8 122 (2022)
  29. How the 26S Proteasome Degrades Ubiquitinated Proteins in the Cell. Coll-Martínez B, Crosas B. Biomolecules 9 (2019)
  30. Hsp100 Molecular Chaperone ClpB and Its Role in Virulence of Bacterial Pathogens. Kędzierska-Mieszkowska S, Zolkiewski M. Int J Mol Sci 22 5319 (2021)
  31. Microtubule-severing enzymes: From cellular functions to molecular mechanism. McNally FJ, Roll-Mecak A. J. Cell Biol. 217 4057-4069 (2018)
  32. Mitochondrial AAA proteases: A stairway to degradation. Steele TE, Glynn SE. Mitochondrion 49 121-127 (2019)
  33. Molecular Mechanisms of TDP-43 Misfolding and Pathology in Amyotrophic Lateral Sclerosis. Prasad A, Bharathi V, Sivalingam V, Girdhar A, Patel BK. Front Mol Neurosci 12 25 (2019)
  34. Protein quality control in the secretory pathway. Sun Z, Brodsky JL. J. Cell Biol. 218 3171-3187 (2019)
  35. Protein quality control: from mechanism to disease : EMBO Workshop, Costa de la Calma (Mallorca), Spain, April 28 - May 03, 2019. Kampinga HH, Mayer MP, Mogk A. Cell Stress Chaperones 24 1013-1026 (2019)
  36. Reversible protein assemblies in the proteostasis network in health and disease. Kohler V, Andréasson C. Front Mol Biosci 10 1155521 (2023)
  37. Shaping the Nascent Ribosome: AAA-ATPases in Eukaryotic Ribosome Biogenesis. Prattes M, Lo YH, Bergler H, Stanley RE. Biomolecules 9 (2019)
  38. Structural insights of the p97/VCP AAA+ ATPase: How adapter interactions coordinate diverse cellular functionality. Braxton JR, Southworth DR. J Biol Chem 299 105182 (2023)
  39. The Role of Malaria Parasite Heat Shock Proteins in Protein Trafficking and Remodelling of Red Blood Cells. Jonsdottir TK, Gabriela M, Gilson PR. Adv Exp Med Biol 1340 141-167 (2021)
  40. Unzipping the Secrets of Amyloid Disassembly by the Human Disaggregase. Franco A, Velasco-Carneros L, Alvarez N, Orozco N, Moro F, Prado A, Muga A. Cells 10 2745 (2021)

Articles citing this publication (102)

  1. A Ycf2-FtsHi Heteromeric AAA-ATPase Complex Is Required for Chloroplast Protein Import. Kikuchi S, Asakura Y, Imai M, Nakahira Y, Kotani Y, Hashiguchi Y, Nakai Y, Takafuji K, Bédard J, Hirabayashi-Ishioka Y, Mori H, Shiina T, Nakai M. Plant Cell 30 2677-2703 (2018)
  2. An allosteric network in spastin couples multiple activities required for microtubule severing. Sandate CR, Szyk A, Zehr EA, Lander GC, Roll-Mecak A. Nat Struct Mol Biol 26 671-678 (2019)
  3. Structure of the mitochondrial inner membrane AAA+ protease YME1 gives insight into substrate processing. Puchades C, Rampello AJ, Shin M, Giuliano CJ, Wiseman RL, Glynn SE, Lander GC. Science 358 (2017)
  4. Structure of the Cdc48 segregase in the act of unfolding an authentic substrate. Cooney I, Han H, Stewart MG, Carson RH, Hansen DT, Iwasa JH, Price JC, Hill CP, Shen PS. Science 365 502-505 (2019)
  5. Structures of AAA protein translocase Bcs1 suggest translocation mechanism of a folded protein. Tang WK, Borgnia MJ, Hsu AL, Esser L, Fox T, de Val N, Xia D. Nat Struct Mol Biol 27 202-209 (2020)
  6. HORMA Domain Proteins and a Trip13-like ATPase Regulate Bacterial cGAS-like Enzymes to Mediate Bacteriophage Immunity. Ye Q, Lau RK, Mathews IT, Birkholz EA, Watrous JD, Azimi CS, Pogliano J, Jain M, Corbett KD. Mol Cell 77 709-722.e7 (2020)
  7. Mechanism for remodelling of the cell cycle checkpoint protein MAD2 by the ATPase TRIP13. Alfieri C, Chang L, Barford D. Nature 559 274-278 (2018)
  8. Structural and kinetic basis for the regulation and potentiation of Hsp104 function. Ye X, Lin J, Mayne L, Shorter J, Englander SW. Proc Natl Acad Sci U S A 117 9384-9392 (2020)
  9. Substrate-engaged 26S proteasome structures reveal mechanisms for ATP-hydrolysis-driven translocation. de la Peña AH, Goodall EA, Gates SN, Lander GC, Martin A. Science 362 (2018)
  10. Malaria parasite translocon structure and mechanism of effector export. Ho CM, Beck JR, Lai M, Cui Y, Goldberg DE, Egea PF, Zhou ZH. Nature 561 70-75 (2018)
  11. Unique Structural Features of the Mitochondrial AAA+ Protease AFG3L2 Reveal the Molecular Basis for Activity in Health and Disease. Puchades C, Ding B, Song A, Wiseman RL, Lander GC, Glynn SE. Mol Cell 75 1073-1085.e6 (2019)
  12. Cryo-EM structures and dynamics of substrate-engaged human 26S proteasome. Dong Y, Zhang S, Wu Z, Li X, Wang WL, Zhu Y, Stoilova-McPhie S, Lu Y, Finley D, Mao Y. Nature 565 49-55 (2019)
  13. A processive rotary mechanism couples substrate unfolding and proteolysis in the ClpXP degradation machinery. Ripstein ZA, Vahidi S, Houry WA, Rubinstein JL, Kay LE. Elife 9 (2020)
  14. Structural principles of SNARE complex recognition by the AAA+ protein NSF. White KI, Zhao M, Choi UB, Pfuetzner RA, Brunger AT. Elife 7 (2018)
  15. Structure of the human clamp loader reveals an autoinhibited conformation of a substrate-bound AAA+ switch. Gaubitz C, Liu X, Magrino J, Stone NP, Landeck J, Hedglin M, Kelch BA. Proc Natl Acad Sci U S A 117 23571-23580 (2020)
  16. Structures of the human LONP1 protease reveal regulatory steps involved in protease activation. Shin M, Watson ER, Song AS, Mindrebo JT, Novick SJ, Griffin PR, Wiseman RL, Lander GC. Nat Commun 12 3239 (2021)
  17. Modular and coordinated activity of AAA+ active sites in the double-ring ClpA unfoldase of the ClpAP protease. Zuromski KL, Sauer RT, Baker TA. Proc Natl Acad Sci U S A 117 25455-25463 (2020)
  18. Expanded Coverage of the 26S Proteasome Conformational Landscape Reveals Mechanisms of Peptidase Gating. Eisele MR, Reed RG, Rudack T, Schweitzer A, Beck F, Nagy I, Pfeifer G, Plitzko JM, Baumeister W, Tomko RJ, Sakata E. Cell Rep 24 1301-1315.e5 (2018)
  19. Structures of the ATP-fueled ClpXP proteolytic machine bound to protein substrate. Fei X, Bell TA, Jenni S, Stinson BM, Baker TA, Harrison SC, Sauer RT. Elife 9 (2020)
  20. Drivers of Hsp104 potentiation revealed by scanning mutagenesis of the middle domain. Ryan JJ, Bao A, Bell B, Ling C, Jackrel ME. Protein Sci 30 1667-1685 (2021)
  21. Heat shock protein 104 (HSP104) chaperones soluble Tau via a mechanism distinct from its disaggregase activity. Zhang X, Zhang S, Zhang L, Lu J, Zhao C, Luo F, Li D, Li X, Liu C. J Biol Chem 294 4956-4965 (2019)
  22. Hinge-Linker Elements in the AAA+ Protein Unfoldase ClpX Mediate Intersubunit Communication, Assembly, and Mechanical Activity. Bell TA, Baker TA, Sauer RT. Biochemistry 57 6787-6796 (2018)
  23. MitoStores: chaperone-controlled protein granules store mitochondrial precursors in the cytosol. Krämer L, Dalheimer N, Räschle M, Storchová Z, Pielage J, Boos F, Herrmann JM. EMBO J 42 e112309 (2023)
  24. Structural asymmetry governs the assembly and GTPase activity of McrBC restriction complexes. Niu Y, Suzuki H, Hosford CJ, Walz T, Chappie JS. Nat Commun 11 5907 (2020)
  25. BacPROTACs mediate targeted protein degradation in bacteria. Morreale FE, Kleine S, Leodolter J, Junker S, Hoi DM, Ovchinnikov S, Okun A, Kley J, Kurzbauer R, Junk L, Guha S, Podlesainski D, Kazmaier U, Boehmelt G, Weinstabl H, Rumpel K, Schmiedel VM, Hartl M, Haselbach D, Meinhart A, Kaiser M, Clausen T. Cell 185 2338-2353.e18 (2022)
  26. Cryo-EM structures of the archaeal PAN-proteasome reveal an around-the-ring ATPase cycle. Majumder P, Rudack T, Beck F, Danev R, Pfeifer G, Nagy I, Baumeister W. Proc. Natl. Acad. Sci. U.S.A. 116 534-539 (2019)
  27. Dynamic structural states of ClpB involved in its disaggregation function. Uchihashi T, Watanabe YH, Nakazaki Y, Yamasaki T, Watanabe H, Maruno T, Ishii K, Uchiyama S, Song C, Murata K, Iino R, Ando T. Nat Commun 9 2147 (2018)
  28. Engineered protein disaggregases mitigate toxicity of aberrant prion-like fusion proteins underlying sarcoma. Ryan JJ, Sprunger ML, Holthaus K, Shorter J, Jackrel ME. J Biol Chem 294 11286-11296 (2019)
  29. Katanin Grips the β-Tubulin Tail through an Electropositive Double Spiral to Sever Microtubules. Zehr EA, Szyk A, Szczesna E, Roll-Mecak A. Dev Cell 52 118-131.e6 (2020)
  30. Molecular basis for ATPase-powered substrate translocation by the Lon AAA+ protease. Li S, Hsieh KY, Su SC, Pintilie GD, Zhang K, Chang CI. J Biol Chem 101239 (2021)
  31. Regulatory coiled-coil domains promote head-to-head assemblies of AAA+ chaperones essential for tunable activity control. Carroni M, Franke KB, Maurer M, Jäger J, Hantke I, Gloge F, Linder D, Gremer S, Turgay K, Bukau B, Mogk A. Elife 6 (2017)
  32. Reversible inhibition of the ClpP protease via an N-terminal conformational switch. Vahidi S, Ripstein ZA, Bonomi M, Yuwen T, Mabanglo MF, Juravsky JB, Rizzolo K, Velyvis A, Houry WA, Vendruscolo M, Rubinstein JL, Kay LE. Proc. Natl. Acad. Sci. U.S.A. 115 E6447-E6456 (2018)
  33. Structural basis of nucleosome assembly by the Abo1 AAA+ ATPase histone chaperone. Cho C, Jang J, Kang Y, Watanabe H, Uchihashi T, Kim SJ, Kato K, Lee JY, Song JJ. Nat Commun 10 5764 (2019)
  34. Overlapping and Specific Functions of the Hsp104 N Domain Define Its Role in Protein Disaggregation. Lee J, Sung N, Mercado JM, Hryc CF, Chang C, Lee S, Tsai FTF. Sci Rep 7 11184 (2017)
  35. Potentiating Hsp104 activity via phosphomimetic mutations in the middle domain. Tariq A, Lin J, Noll MM, Torrente MP, Mack KL, Murillo OH, Jackrel ME, Shorter J. FEMS Yeast Res. 18 (2018)
  36. Skd3 (human ClpB) is a potent mitochondrial protein disaggregase that is inactivated by 3-methylglutaconic aciduria-linked mutations. Cupo RR, Shorter J. Elife 9 (2020)
  37. Structural insights into ATP hydrolysis by the MoxR ATPase RavA and the LdcI-RavA cage-like complex. Jessop M, Arragain B, Miras R, Fraudeau A, Huard K, Bacia-Verloop M, Catty P, Felix J, Malet H, Gutsche I. Commun Biol 3 46 (2020)
  38. A lipid gating mechanism for the channel-forming O antigen ABC transporter. Caffalette CA, Corey RA, Sansom MSP, Stansfeld PJ, Zimmer J. Nat Commun 10 824 (2019)
  39. AAA+ protease-adaptor structures reveal altered conformations and ring specialization. Kim S, Fei X, Sauer RT, Baker TA. Nat Struct Mol Biol 29 1068-1079 (2022)
  40. Chain Entropy Beats Hydrogen Bonds to Unfold and Thread Dialcohol Phosphates inside Cyanostar Macrocycles To Form [3]Pseudorotaxanes. Fadler RE, Al Ouahabi A, Qiao B, Carta V, König NF, Gao X, Zhao W, Zhang Y, Lutz JF, Flood AH. J Org Chem 86 4532-4546 (2021)
  41. Class-specific interactions between Sis1 J-domain protein and Hsp70 chaperone potentiate disaggregation of misfolded proteins. Wyszkowski H, Janta A, Sztangierska W, Obuchowski I, Chamera T, Kłosowska A, Liberek K. Proc Natl Acad Sci U S A 118 e2108163118 (2021)
  42. Comprehensive structural characterization of the human AAA+ disaggregase CLPB in the apo- and substrate-bound states reveals a unique mode of action driven by oligomerization. Wu D, Liu Y, Dai Y, Wang G, Lu G, Chen Y, Li N, Lin J, Gao N. PLoS Biol 21 e3001987 (2023)
  43. Conserved structural elements specialize ATAD1 as a membrane protein extraction machine. Wang L, Toutkoushian H, Belyy V, Kokontis CY, Walter P. Elife 11 e73941 (2022)
  44. Cryo-EM Structures of the Hsp104 Protein Disaggregase Captured in the ATP Conformation. Lee S, Roh SH, Lee J, Sung N, Liu J, Tsai FTF. Cell Rep 26 29-36.e3 (2019)
  45. Electrostatic interactions between middle domain motif-1 and the AAA1 module of the bacterial ClpB chaperone are essential for protein disaggregation. Sugita S, Watanabe K, Hashimoto K, Niwa T, Uemura E, Taguchi H, Watanabe YH. J. Biol. Chem. 293 19228-19239 (2018)
  46. Entropic Inhibition: How the Activity of a AAA+ Machine Is Modulated by Its Substrate-Binding Domain. Iljina M, Mazal H, Goloubinoff P, Riven I, Haran G. ACS Chem Biol 16 775-785 (2021)
  47. Hsp104 and Potentiated Variants Can Operate as Distinct Nonprocessive Translocases. Durie CL, Lin J, Scull NW, Mack KL, Jackrel ME, Sweeny EA, Castellano LM, Shorter J, Lucius AL. Biophys J 116 1856-1872 (2019)
  48. Interaction of substrate-mimicking peptides with the AAA+ ATPase ClpB from Escherichia coli. Ranaweera CB, Glaza P, Yang T, Zolkiewski M. Arch. Biochem. Biophys. 655 12-17 (2018)
  49. Kinetic Analysis of AAA+ Translocases by Combined Fluorescence and Anisotropy Methods. Scull NW, Lucius AL. Biophys J 119 1335-1350 (2020)
  50. Quantitative NMR analysis of the mechanism and kinetics of chaperone Hsp104 action on amyloid-β42 aggregation and fibril formation. Ghosh S, Tugarinov V, Clore GM. Proc Natl Acad Sci U S A 120 e2305823120 (2023)
  51. Reconstruction of Three-Dimensional Conformations of Bacterial ClpB from High-Speed Atomic-Force-Microscopy Images. Dasgupta B, Miyashita O, Uchihashi T, Tama F. Front Mol Biosci 8 704274 (2021)
  52. Structural basis for aggregate dissolution and refolding by the Mycobacterium tuberculosis ClpB-DnaK bi-chaperone system. Yin Y, Feng X, Yu H, Fay A, Kovach A, Glickman MS, Li H. Cell Rep 35 109166 (2021)
  53. Structural basis for distinct operational modes and protease activation in AAA+ protease Lon. Shin M, Puchades C, Asmita A, Puri N, Adjei E, Wiseman RL, Karzai AW, Lander GC. Sci Adv 6 eaba8404 (2020)
  54. Structural determinants for protein unfolding and translocation by the Hsp104 protein disaggregase. Lee J, Sung N, Yeo L, Chang C, Lee S, Tsai FTF. Biosci. Rep. 37 (2017)
  55. Structure of a Tc holotoxin pore provides insights into the translocation mechanism. Roderer D, Hofnagel O, Benz R, Raunser S. Proc. Natl. Acad. Sci. U.S.A. 116 23083-23090 (2019)
  56. Structure of spastin bound to a glutamate-rich peptide implies a hand-over-hand mechanism of substrate translocation. Han H, Schubert HL, McCullough J, Monroe N, Purdy MD, Yeager M, Sundquist WI, Hill CP. J Biol Chem 295 435-443 (2020)
  57. Structure of the AAA protein Msp1 reveals mechanism of mislocalized membrane protein extraction. Wang L, Myasnikov A, Pan X, Walter P. Elife 9 (2020)
  58. Structures and operating principles of the replisome. Gao Y, Cui Y, Fox T, Lin S, Wang H, de Val N, Zhou ZH, Yang W. Science 363 (2019)
  59. The CryoEM structure of the Saccharomyces cerevisiae ribosome maturation factor Rea1. Sosnowski P, Urnavicius L, Boland A, Fagiewicz R, Busselez J, Papai G, Schmidt H. Elife 7 (2018)
  60. The p97/VCP adaptor UBXD1 drives AAA+ remodeling and ring opening through multi-domain tethered interactions. Braxton JR, Altobelli CR, Tucker MR, Tse E, Thwin AC, Arkin MR, Southworth DR. Nat Struct Mol Biol 30 2009-2019 (2023)
  61. Uncoupling the Threading and Unfoldase Actions of Plasmodium HSP101 Reveals Differences in Export between Soluble and Insoluble Proteins. Matthews KM, Kalanon M, de Koning-Ward TF. MBio 10 (2019)
  62. ATAD3A has a scaffolding role regulating mitochondria inner membrane structure and protein assembly. Arguello T, Peralta S, Antonicka H, Gaidosh G, Diaz F, Tu YT, Garcia S, Shiekhattar R, Barrientos A, Moraes CT. Cell Rep 37 110139 (2021)
  63. ATP hydrolysis tunes specificity of a AAA+ protease. Mahmoud SA, Aldikacti B, Chien P. Cell Rep 40 111405 (2022)
  64. Chaperones directly and efficiently disperse stress-triggered biomolecular condensates. Yoo H, Bard JAM, Pilipenko EV, Drummond DA. Mol Cell 82 741-755.e11 (2022)
  65. Cryo-EM structure of the ClpXP protein degradation machinery. Gatsogiannis C, Balogh D, Merino F, Sieber SA, Raunser S. Nat. Struct. Mol. Biol. 26 946-954 (2019)
  66. Cryo-EM structure of the essential ribosome assembly AAA-ATPase Rix7. Lo YH, Sobhany M, Hsu AL, Ford BL, Krahn JM, Borgnia MJ, Stanley RE. Nat Commun 10 513 (2019)
  67. Crystal structure of the catalytic D2 domain of the AAA+ ATPase p97 reveals a putative helical split-washer-type mechanism for substrate unfolding. Stach L, Morgan RM, Makhlouf L, Douangamath A, von Delft F, Zhang X, Freemont PS. FEBS Lett 594 933-943 (2020)
  68. Deciphering the mechanism and function of Hsp100 unfoldases from protein structure. Lee G, Kim RS, Lee SB, Lee S, Tsai FTF. Biochem Soc Trans 50 1725-1736 (2022)
  69. Dodecamer assembly of a metazoan AAA+ chaperone couples substrate extraction to refolding. Gupta A, Lentzsch AM, Siegel A, Yu Z, Chio US, Cheng Y, Shan SO. Sci Adv 9 eadf5336 (2023)
  70. Dynamic 3D proteomes reveal protein functional alterations at high resolution in situ. Cappelletti V, Hauser T, Piazza I, Pepelnjak M, Malinovska L, Fuhrer T, Li Y, Dörig C, Boersema P, Gillet L, Grossbach J, Dugourd A, Saez-Rodriguez J, Beyer A, Zamboni N, Caflisch A, de Souza N, Picotti P. Cell 184 545-559.e22 (2021)
  71. Editorial Editorial: The Role of AAA+ Proteins in Protein Repair and Degradation. Shorter J, Houry WA. Front Mol Biosci 5 85 (2018)
  72. Factors underlying asymmetric pore dynamics of disaggregase and microtubule-severing AAA+ machines. Damre M, Dayananda A, Varikoti RA, Stan G, Dima RI. Biophys J 120 3437-3454 (2021)
  73. Fluorescence Methods Applied to the Description of Urea-Dependent YME1L Protease Unfolding. Moore S, Pickens A, Rodriguez JL, Marsee JD, Miller JM. Biomolecules 10 (2020)
  74. Functional analysis of proposed substrate-binding residues of Hsp104. Howard MK, Sohn BS, von Borcke J, Xu A, Jackrel ME. PLoS One 15 e0230198 (2020)
  75. Hsp104 N-terminal domain interaction with substrates plays a regulatory role in protein disaggregation. Harari A, Zoltsman G, Levin T, Rosenzweig R. FEBS J 289 5359-5377 (2022)
  76. Huntingtin Polyglutamine Fragments Are a Substrate for Hsp104 in Saccharomyces cerevisiae. Wayne NJ, Dembny KE, Pease T, Saba F, Zhao X, Masison DC, Greene LE. Mol Cell Biol 41 e0012221 (2021)
  77. Interactions between a subset of substrate side chains and AAA+ motor pore loops determine grip during protein unfolding. Bell TA, Baker TA, Sauer RT. Elife 8 (2019)
  78. Mycobacterium tuberculosis ClpC1 N-Terminal Domain Is Dispensable for Adaptor Protein-Dependent Allosteric Regulation. Marsee JD, Ridings A, Yu T, Miller JM. Int J Mol Sci 19 (2018)
  79. Nuclear Hsp104 safeguards the dormant translation machinery during quiescence. Kohler V, Kohler A, Berglund LL, Hao X, Gersing S, Imhof A, Nyström T, Höög JL, Ott M, Andréasson C, Büttner S. Nat Commun 15 315 (2024)
  80. Omnipresent Maxwell's demons orchestrate information management in living cells. Boël G, Danot O, de Lorenzo V, Danchin A. Microb Biotechnol 12 210-242 (2019)
  81. Probing the drivers of Staphylococcus aureus biofilm protein amyloidogenesis and disrupting biofilms with engineered protein disaggregases. Howard MK, Miller KR, Sohn BS, Ryan JJ, Xu A, Jackrel ME. mBio 14 e0058723 (2023)
  82. Rearranging AAA+ architecture to accommodate folded substrates. Shen PS. Nat Struct Mol Biol 27 225-226 (2020)
  83. Role of ClpB From Corynebacterium crenatum in Thermal Stress and Arginine Fermentation. Huang M, Zhao Y, Feng L, Zhu L, Zhan L, Chen X. Front Microbiol 11 1660 (2020)
  84. Rubisco activase requires residues in the large subunit N terminus to remodel inhibited plant Rubisco. Ng J, Guo Z, Mueller-Cajar O. J Biol Chem 295 16427-16435 (2020)
  85. Significance of Individual Domains of ClpL: A Novel Chaperone from Streptococcus mutans. Jana B, Biswas I. Biochemistry 59 3368-3379 (2020)
  86. Single-molecule analysis reveals rotational substeps and chemo-mechanical coupling scheme of Enterococcus hirae V1-ATPase. Iida T, Minagawa Y, Ueno H, Kawai F, Murata T, Iino R. J. Biol. Chem. 294 17017-17030 (2019)
  87. Structural basis for substrate gripping and translocation by the ClpB AAA+ disaggregase. Rizo AN, Lin J, Gates SN, Tse E, Bart SM, Castellano LM, DiMaio F, Shorter J, Southworth DR. Nat Commun 10 2393 (2019)
  88. Structural dynamics of AAA + ATPase Drg1 and mechanism of benzo-diazaborine inhibition. Ma C, Wu D, Chen Q, Gao N. Nat Commun 13 6765 (2022)
  89. Structural snapshots of the cellular folded protein translocation machinery Bcs1. Xia D. FEBS J 288 2870-2883 (2021)
  90. Structure of Vps4 with circular peptides and implications for translocation of two polypeptide chains by AAA+ ATPases. Han H, Fulcher JM, Dandey VP, Iwasa JH, Sundquist WI, Kay MS, Shen PS, Hill CP. Elife 8 (2019)
  91. Structure of the human ATAD2 AAA+ histone chaperone reveals mechanism of regulation and inter-subunit communication. Cho C, Ganser C, Uchihashi T, Kato K, Song JJ. Commun Biol 6 993 (2023)
  92. Structure-based mechanism for activation of the AAA+ GTPase McrB by the endonuclease McrC. Nirwan N, Itoh Y, Singh P, Bandyopadhyay S, Vinothkumar KR, Amunts A, Saikrishnan K. Nat Commun 10 3058 (2019)
  93. The Impact of Hidden Structure on Aggregate Disassembly by Molecular Chaperones. Shoup D, Roth A, Puchalla J, Rye HS. Front Mol Biosci 9 915307 (2022)
  94. The Mutability of Yeast Prions. King CY. Viruses 14 2337 (2022)
  95. The force required to remove tubulin from the microtubule lattice by pulling on its α-tubulin C-terminal tail. Kuo YW, Mahamdeh M, Tuna Y, Howard J. Nat Commun 13 3651 (2022)
  96. The huntingtin inclusion is a dynamic phase-separated compartment. Aktar F, Burudpakdee C, Polanco M, Pei S, Swayne TC, Lipke PN, Emtage L. Life Sci Alliance 2 (2019)
  97. Therapeutic genetic variation revealed in diverse Hsp104 homologs. March ZM, Sweeney K, Kim H, Yan X, Castellano LM, Jackrel ME, Lin J, Chuang E, Gomes E, Willicott CW, Michalska K, Jedrzejczak RP, Joachimiak A, Caldwell KA, Caldwell GA, Shalem O, Shorter J. Elife 9 (2020)
  98. Tunable microsecond dynamics of an allosteric switch regulate the activity of a AAA+ disaggregation machine. Mazal H, Iljina M, Barak Y, Elad N, Rosenzweig R, Goloubinoff P, Riven I, Haran G. Nat Commun 10 1438 (2019)
  99. Tuning Hsp104 specificity to selectively detoxify α-synuclein. Mack KL, Kim H, Barbieri EM, Lin J, Braganza S, Jackrel ME, DeNizio JE, Yan X, Chuang E, Tariq A, Cupo RR, Castellano LM, Caldwell KA, Caldwell GA, Shorter J. Mol Cell 83 3314-3332.e9 (2023)
  100. Two-Step Activation Mechanism of the ClpB Disaggregase for Sequential Substrate Threading by the Main ATPase Motor. Deville C, Franke K, Mogk A, Bukau B, Saibil HR. Cell Rep 27 3433-3446.e4 (2019)
  101. Ultrafast pore-loop dynamics in a AAA+ machine point to a Brownian-ratchet mechanism for protein translocation. Mazal H, Iljina M, Riven I, Haran G. Sci Adv 7 eabg4674 (2021)
  102. Unique structural features govern the activity of a human mitochondrial AAA+ disaggregase, Skd3. Cupo RR, Rizo AN, Braun GA, Tse E, Chuang E, Gupta K, Southworth DR, Shorter J. Cell Rep 40 111408 (2022)


Quick links