1doa Citations

Structure of the Rho family GTP-binding protein Cdc42 in complex with the multifunctional regulator RhoGDI.

Cell 100 345-56 (2000)
Cited: 310 times
EuropePMC logo PMID: 10676816

Abstract

The RhoGDI proteins serve as key multifunctional regulators of Rho family GTP-binding proteins. The 2.6 A X-ray crystallographic structure of the Cdc42/RhoGDI complex reveals two important sites of interaction between GDI and Cdc42. First, the amino-terminal regulatory arm of the GDI binds to the switch I and II domains of Cdc42 leading to the inhibition of both GDP dissociation and GTP hydrolysis. Second, the geranylgeranyl moiety of Cdc42 inserts into a hydrophobic pocket within the immunoglobulin-like domain of the GDI molecule leading to membrane release. The structural data demonstrate how GDIs serve as negative regulators of small GTP-binding proteins and how the isoprenoid moiety is utilized in this critical regulatory interaction.

Reviews - 1doa mentioned but not cited (2)

  1. Always look on the bright site of Rho: structural implications for a conserved intermolecular interface. Dvorsky R, Ahmadian MR. EMBO Rep. 5 1130-1136 (2004)
  2. Progress in the therapeutic inhibition of Cdc42 signalling. Murphy NP, Mott HR, Owen D. Biochem Soc Trans 49 1443-1456 (2021)

Articles - 1doa mentioned but not cited (24)



Reviews citing this publication (82)

  1. Small GTP-binding proteins. Takai Y, Sasaki T, Matozaki T. Physiol. Rev. 81 153-208 (2001)
  2. Rho GTPases and their effector proteins. Bishop AL, Hall A. Biochem. J. 348 Pt 2 241-255 (2000)
  3. Clostridium difficile toxins: mechanism of action and role in disease. Voth DE, Ballard JD. Clin. Microbiol. Rev. 18 247-263 (2005)
  4. Regulation of small GTPases by GEFs, GAPs, and GDIs. Cherfils J, Zeghouf M. Physiol. Rev. 93 269-309 (2013)
  5. GDIs: central regulatory molecules in Rho GTPase activation. DerMardirossian C, Bokoch GM. Trends Cell Biol. 15 356-363 (2005)
  6. Regulation of Nox and Duox enzymatic activity and expression. Lambeth JD, Kawahara T, Diebold B. Free Radic. Biol. Med. 43 319-331 (2007)
  7. Trafficking and signaling by fatty-acylated and prenylated proteins. Resh MD. Nat. Chem. Biol. 2 584-590 (2006)
  8. Activation and assembly of the NADPH oxidase: a structural perspective. Groemping Y, Rittinger K. Biochem. J. 386 401-416 (2005)
  9. Central roles of small GTPases in the development of cell polarity in yeast and beyond. Park HO, Bi E. Microbiol. Mol. Biol. Rev. 71 48-96 (2007)
  10. The 'invisible hand': regulation of RHO GTPases by RHOGDIs. Garcia-Mata R, Boulter E, Burridge K. Nat. Rev. Mol. Cell Biol. 12 493-504 (2011)
  11. Post-translational modifications and regulation of the RAS superfamily of GTPases as anticancer targets. Konstantinopoulos PA, Karamouzis MV, Papavassiliou AG. Nat Rev Drug Discov 6 541-555 (2007)
  12. Assembly of the phagocyte NADPH oxidase. Nauseef WM. Histochem. Cell Biol. 122 277-291 (2004)
  13. Rho GTPases, dendritic structure, and mental retardation. Newey SE, Velamoor V, Govek EE, Van Aelst L. J. Neurobiol. 64 58-74 (2005)
  14. RhoGDI: multiple functions in the regulation of Rho family GTPase activities. Dovas A, Couchman JR. Biochem. J. 390 1-9 (2005)
  15. Regulating the regulator: post-translational modification of RAS. Ahearn IM, Haigis K, Bar-Sagi D, Philips MR. Nat. Rev. Mol. Cell Biol. 13 39-51 (2011)
  16. Thematic review series: lipid posttranslational modifications. CAAX modification and membrane targeting of Ras. Wright LP, Philips MR. J. Lipid Res. 47 883-891 (2006)
  17. Structure-function relationships of the G domain, a canonical switch motif. Wittinghofer A, Vetter IR. Annu. Rev. Biochem. 80 943-971 (2011)
  18. Thematic review series: lipid posttranslational modifications. Structural biology of protein farnesyltransferase and geranylgeranyltransferase type I. Lane KT, Beese LS. J. Lipid Res. 47 681-699 (2006)
  19. The polybasic region of Ras and Rho family small GTPases: a regulator of protein interactions and membrane association and a site of nuclear localization signal sequences. Williams CL. Cell. Signal. 15 1071-1080 (2003)
  20. Regulating Rho GTPases and their regulators. Hodge RG, Ridley AJ. Nat. Rev. Mol. Cell Biol. 17 496-510 (2016)
  21. Therapeutic intervention based on protein prenylation and associated modifications. Gelb MH, Brunsveld L, Hrycyna CA, Michaelis S, Tamanoi F, Van Voorhis WC, Waldmann H. Nat. Chem. Biol. 2 518-528 (2006)
  22. ROCK and Rho: biochemistry and neuronal functions of Rho-associated protein kinases. Schmandke A, Schmandke A, Strittmatter SM. Neuroscientist 13 454-469 (2007)
  23. The role of Rho GTPase proteins in CNS neuronal migration. Govek EE, Hatten ME, Van Aelst L. Dev Neurobiol 71 528-553 (2011)
  24. The chemical toolbox for monitoring protein fatty acylation and prenylation. Hannoush RN, Sun J. Nat. Chem. Biol. 6 498-506 (2010)
  25. Signaling to the Rho GTPases: networking with the DH domain. Hoffman GR, Cerione RA. FEBS Lett. 513 85-91 (2002)
  26. Protein prenylation: unique fats make their mark on biology. Wang M, Casey PJ. Nat. Rev. Mol. Cell Biol. 17 110-122 (2016)
  27. Supervised membrane swimming: small G-protein lifeguards regulate PIPK signalling and monitor intracellular PtdIns(4,5)P2 pools. Santarius M, Lee CH, Anderson RA. Biochem. J. 398 1-13 (2006)
  28. RhoGDIs revisited: novel roles in Rho regulation. Dransart E, Olofsson B, Cherfils J. Traffic 6 957-966 (2005)
  29. C3 exoenzymes, novel insights into structure and action of Rho-ADP-ribosylating toxins. Vogelsgesang M, Pautsch A, Aktories K. Naunyn Schmiedebergs Arch. Pharmacol. 374 347-360 (2007)
  30. Regulators of Rho GTPases in neuronal development. Watabe-Uchida M, Govek EE, Van Aelst L. J. Neurosci. 26 10633-10635 (2006)
  31. The many faces of Ras: recognition of small GTP-binding proteins. Corbett KD, Alber T. Trends Biochem. Sci. 26 710-716 (2001)
  32. The cytotoxic necrotizing factor 1 (CNF1) from Escherichia coli. Boquet P. Toxicon 39 1673-1680 (2001)
  33. The role of small GTPases in neuronal morphogenesis and polarity. Gonzalez-Billault C, Muñoz-Llancao P, Henriquez DR, Wojnacki J, Conde C, Caceres A. Cytoskeleton (Hoboken) 69 464-485 (2012)
  34. Bacterial guanine nucleotide exchange factors SopE-like and WxxxE effectors. Bulgin R, Raymond B, Garnett JA, Frankel G, Crepin VF, Berger CN, Arbeloa A. Infect. Immun. 78 1417-1425 (2010)
  35. Cellular and molecular features of axon collaterals and dendrites. Acebes A, Ferrús A. Trends Neurosci. 23 557-565 (2000)
  36. Structure and function of Rho-type molecular switches in plants. Berken A, Wittinghofer A. Plant Physiol. Biochem. 46 380-393 (2008)
  37. GTPases involved in vesicular trafficking: structures and mechanisms. Itzen A, Goody RS. Semin. Cell Dev. Biol. 22 48-56 (2011)
  38. Regulation of Rho proteins by phosphorylation in the cardiovascular system. Loirand G, Guilluy C, Pacaud P. Trends Cardiovasc. Med. 16 199-204 (2006)
  39. Genetically Encoded Fluorescent Biosensors Illuminate the Spatiotemporal Regulation of Signaling Networks. Greenwald EC, Mehta S, Zhang J. Chem Rev 118 11707-11794 (2018)
  40. Protein Interactions at Endothelial Junctions and Signaling Mechanisms Regulating Endothelial Permeability. Komarova YA, Kruse K, Mehta D, Malik AB. Circ. Res. 120 179-206 (2017)
  41. Role of the Rho GTPase Rac in the activation of the phagocyte NADPH oxidase: outsourcing a key task. Pick E. Small GTPases 5 e27952 (2014)
  42. Toward understanding RhoGTPase specificity: structure, function and local activation. Schaefer A, Reinhard NR, Hordijk PL. Small GTPases 5 6 (2014)
  43. Signal transduction pathways regulated by Rho GTPases in Dictyostelium. Rivero F, Somesh BP. J. Muscle Res. Cell. Motil. 23 737-749 (2002)
  44. Structures of Ras superfamily effector complexes: What have we learnt in two decades? Mott HR, Owen D. Crit. Rev. Biochem. Mol. Biol. 50 85-133 (2015)
  45. RHO GTPase signaling for axon extension: is prenylation important? Samuel F, Hynds DL. Mol. Neurobiol. 42 133-142 (2010)
  46. The prenyl-binding protein PrBP/δ: a chaperone participating in intracellular trafficking. Zhang H, Constantine R, Frederick JM, Baehr W. Vision Res. 75 19-25 (2012)
  47. Inhibition and termination of physiological responses by GTPase activating proteins. Ligeti E, Welti S, Scheffzek K. Physiol. Rev. 92 237-272 (2012)
  48. Off the beaten paths: alternative and crosstalk regulation of Rho GTPases. Boulter E, Estrach S, Garcia-Mata R, Féral CC. FASEB J. 26 469-479 (2012)
  49. Nonconventional trafficking of Ras associated with Ras signal organization. Ashery U, Yizhar O, Rotblat B, Kloog Y. Traffic 7 119-126 (2006)
  50. Cdc42: Role in Cancer Management. Qadir MI, Parveen A, Ali M. Chem Biol Drug Des 86 432-439 (2015)
  51. RhoGDI2 as a therapeutic target in cancer. Cho HJ, Baek KE, Yoo J. Expert Opin. Ther. Targets 14 67-75 (2010)
  52. Many roads to symmetry breaking: molecular mechanisms and theoretical models of yeast cell polarity. Goryachev AB, Leda M. Mol. Biol. Cell 28 370-380 (2017)
  53. Understanding Rho/Rac biology in T-cells using animal models. Bustelo XR. Bioessays 24 602-612 (2002)
  54. Protein post-translational modifications: In silico prediction tools and molecular modeling. Audagnotto M, Dal Peraro M. Comput Struct Biotechnol J 15 307-319 (2017)
  55. Small G proteins and their regulators in cellular signalling. Csépányi-Kömi R, Lévay M, Ligeti E. Mol. Cell. Endocrinol. 353 10-20 (2012)
  56. Protein lipid modifications and the regulation of ROP GTPase function. Yalovsky S. J. Exp. Bot. 66 1617-1624 (2015)
  57. Rho GTPases: Novel Players in the Regulation of the DNA Damage Response? Fritz G, Henninger C. Biomolecules 5 2417-2434 (2015)
  58. Regulation of Cdc42 and its effectors in epithelial morphogenesis. Pichaud F, Walther RF, Nunes de Almeida F. J Cell Sci 132 (2019)
  59. Toward a structural understanding of arf family:effector specificity. Chavrier P, Ménétrey J. Structure 18 1552-1558 (2010)
  60. Aberrant Rho GTPases signaling and cognitive dysfunction: in vivo evidence for a compelling molecular relationship. De Filippis B, Romano E, Laviola G. Neurosci Biobehav Rev 46 Pt 2 285-301 (2014)
  61. Genetically encoded intracellular sensors based on fluorescent proteins. Souslova EA, Chudakov DM. Biochemistry Mosc. 72 683-697 (2007)
  62. ROP GTPases Structure-Function and Signaling Pathways. Feiguelman G, Fu Y, Yalovsky S. Plant Physiol. 176 57-79 (2018)
  63. The RHO Family GTPases: Mechanisms of Regulation and Signaling. Mosaddeghzadeh N, Ahmadian MR. Cells 10 1831 (2021)
  64. RHO protein regulation of contraction in the human uterus. Lartey J, López Bernal A. Reproduction 138 407-424 (2009)
  65. Galectins as Molecular Targets for Therapeutic Intervention. Dings RPM, Miller MC, Griffin RJ, Mayo KH. Int J Mol Sci 19 (2018)
  66. How Bacteria Subvert Animal Cell Structure and Function. Jimenez A, Chen D, Alto NM. Annu. Rev. Cell Dev. Biol. 32 373-397 (2016)
  67. Post-translational modification of RAS proteins. Campbell SL, Philips MR. Curr Opin Struct Biol 71 180-192 (2021)
  68. Chaperone-mediated specificity in Ras and Rap signaling. Azoulay-Alfaguter I, Strazza M, Mor A. Crit. Rev. Biochem. Mol. Biol. 50 194-202 (2015)
  69. Sorting of lipidated cargo by the Arl2/Arl3 system. Fansa EK, Wittinghofer A. Small GTPases 7 222-230 (2016)
  70. Molecular subversion of Cdc42 signalling in cancer. Murphy NP, Binti Ahmad Mokhtar AM, Mott HR, Owen D. Biochem Soc Trans 49 1425-1442 (2021)
  71. Pleiotropic Roles of Calmodulin in the Regulation of KRas and Rac1 GTPases: Functional Diversity in Health and Disease. Tebar F, Chavero A, Agell N, Lu A, Rentero C, Enrich C, Grewal T. Int J Mol Sci 21 (2020)
  72. Posttranslational Modifications of RAS Proteins. Ahearn I, Zhou M, Philips MR. Cold Spring Harb Perspect Med 8 (2018)
  73. Protein Lipidation As a Regulator of Apoptotic Calcium Release: Relevance to Cancer. Chen JJ, Boehning D. Front Oncol 7 138 (2017)
  74. Regulating Cdc42 and Its Signaling Pathways in Cancer: Small Molecules and MicroRNA as New Treatment Candidates. Xiao XH, Lv LC, Duan J, Wu YM, He SJ, Hu ZZ, Xiong LX. Molecules 23 (2018)
  75. Role of Rho-specific guanine nucleotide dissociation inhibitor α regulation in cell migration. Xie F, Shao S, Aziz AUR, Zhang B, Wang H, Liu B. Acta Histochem. 119 183-189 (2017)
  76. The Rho GTPase signalling pathway in urothelial carcinoma. Woldu SL, Hutchinson RC, Krabbe LM, Sanli O, Margulis V. Nat Rev Urol 15 83-91 (2018)
  77. AIPL1: A specialized chaperone for the phototransduction effector. Yadav RP, Artemyev NO. Cell. Signal. 40 183-189 (2017)
  78. Cell biology of protein-lipid conjugation. Sakamaki JI, Mizushima N. Cell Struct Funct 48 99-112 (2023)
  79. Delta-Catenin as a Modulator of Rho GTPases in Neurons. Donta MS, Srivastava Y, McCrea PD. Front Cell Neurosci 16 939143 (2022)
  80. High Throughput strategies Aimed at Closing the GAP in Our Knowledge of Rho GTPase Signaling. Dahmene M, Quirion L, Laurin M. Cells 9 (2020)
  81. Regulation of Rho GTPases by RhoGDIs in Human Cancers. Cho HJ, Kim JT, Baek KE, Kim BY, Lee HG. Cells 8 (2019)
  82. The Roles of Par3, Par6, and aPKC Polarity Proteins in Normal Neurodevelopment and in Neurodegenerative and Neuropsychiatric Disorders. Zhang L, Wei X. J Neurosci 42 4774-4793 (2022)

Articles citing this publication (202)