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Crystal structure of the human glucose transporter GLUT1.

Deng D, Xu C, Sun P, Wu J, Yan C, Hu M, Yan N
Nature 510 121-5 (2014)
Cited: 384 times
EuropePMC logo PMID: 24847886

Abstract

The glucose transporter GLUT1 catalyses facilitative diffusion of glucose into erythrocytes and is responsible for glucose supply to the brain and other organs. Dysfunctional mutations may lead to GLUT1 deficiency syndrome, whereas overexpression of GLUT1 is a prognostic indicator for cancer. Despite decades of investigation, the structure of GLUT1 remains unknown. Here we report the crystal structure of human GLUT1 at 3.2 Å resolution. The full-length protein, which has a canonical major facilitator superfamily fold, is captured in an inward-open conformation. This structure allows accurate mapping and potential mechanistic interpretation of disease-associated mutations in GLUT1. Structure-based analysis of these mutations provides an insight into the alternating access mechanism of GLUT1 and other members of the sugar porter subfamily. Structural comparison of the uniporter GLUT1 with its bacterial homologue XylE, a proton-coupled xylose symporter, allows examination of the transport mechanisms of both passive facilitators and active transporters.

Reviews - 4pyp mentioned but not cited (15)

  1. GLUT, SGLT, and SWEET: Structural and mechanistic investigations of the glucose transporters. Deng D, Yan N. Protein Sci 25 546-558 (2016)
  2. Carbonic Anhydrases: Role in pH Control and Cancer. Mboge MY, Mahon BP, McKenna R, Frost SC. Metabolites 8 E19 (2018)
  3. Pathways of arsenic uptake and efflux. Garbinski LD, Rosen BP, Chen J. Environ Int 126 585-597 (2019)
  4. The recombinant expression systems for structure determination of eukaryotic membrane proteins. He Y, Wang K, Yan N. Protein Cell 5 658-672 (2014)
  5. Structure, function and regulation of mammalian glucose transporters of the SLC2 family. Holman GD. Pflugers Arch 472 1155-1175 (2020)
  6. Understanding transporter specificity and the discrete appearance of channel-like gating domains in transporters. Diallinas G. Front Pharmacol 5 207 (2014)
  7. Advances and Challenges in Rational Drug Design for SLCs. Garibsingh RA, Schlessinger A. Trends Pharmacol Sci 40 790-800 (2019)
  8. Pharmacological Targeting of GLUT1 to Control Autoreactive T Cell Responses. Di Dedda C, Vignali D, Piemonti L, Monti P. Int J Mol Sci 20 E4962 (2019)
  9. Ligand Screening Systems for Human Glucose Transporters as Tools in Drug Discovery. Schmidl S, Iancu CV, Choe JY, Oreb M. Front Chem 6 183 (2018)
  10. Drug Discovery of Plausible Lead Natural Compounds That Target the Insulin Signaling Pathway: Bioinformatics Approaches. Shanak S, Bassalat N, Barghash A, Kadan S, Ardah M, Zaid H. Evid Based Complement Alternat Med 2022 2832889 (2022)
  11. An overview of the Plasmodium falciparum hexose transporter and its therapeutic interventions. Jiang X. Proteins 90 1766-1778 (2022)
  12. Glycoscience@Synchrotron: Synchrotron radiation applied to structural glycoscience. Pérez S, de Sanctis D. Beilstein J Org Chem 13 1145-1167 (2017)
  13. Hijacked then lost in translation: the plight of the recombinant host cell in membrane protein structural biology projects. Bill RM, von der Haar T. Curr Opin Struct Biol 32 147-155 (2015)
  14. Bacterial effluxome as a barrier against antimicrobial agents: structural biology aspects and drug targeting. Brindangnanam P, Sawant AR, Prashanth K, Coumar MS. Tissue Barriers 10 2013695 (2022)
  15. Ins and Outs of Rocker Switch Mechanism in Major Facilitator Superfamily of Transporters. Sauve S, Williamson J, Polasa A, Moradi M. Membranes (Basel) 13 462 (2023)

Articles - 4pyp mentioned but not cited (74)



Reviews citing this publication (89)

  1. Blood-Brain Barrier: From Physiology to Disease and Back. Sweeney MD, Zhao Z, Montagne A, Nelson AR, Zlokovic BV. Physiol Rev 99 21-78 (2019)
  2. A Call for Systematic Research on Solute Carriers. César-Razquin A, Snijder B, Frappier-Brinton T, Isserlin R, Gyimesi G, Bai X, Reithmeier RA, Hepworth D, Hediger MA, Edwards AM, Superti-Furga G. Cell 162 478-487 (2015)
  3. Shared Molecular Mechanisms of Membrane Transporters. Drew D, Boudker O. Annu Rev Biochem 85 543-572 (2016)
  4. Structural Biology of the Major Facilitator Superfamily Transporters. Yan N. Annu Rev Biophys 44 257-283 (2015)
  5. Glucose transporters in cancer - from tumor cells to the tumor microenvironment. Ancey PB, Contat C, Meylan E. FEBS J 285 2926-2943 (2018)
  6. Transport of sugars. Chen LQ, Cheung LS, Feng L, Tanner W, Frommer WB. Annu Rev Biochem 84 865-894 (2015)
  7. Understanding transport by the major facilitator superfamily (MFS): structures pave the way. Quistgaard EM, Löw C, Guettou F, Nordlund P. Nat Rev Mol Cell Biol 17 123-132 (2016)
  8. Membrane transporters for the special amino acid glutamine: structure/function relationships and relevance to human health. Pochini L, Scalise M, Galluccio M, Indiveri C. Front Chem 2 61 (2014)
  9. Glucose Transporters at the Blood-Brain Barrier: Function, Regulation and Gateways for Drug Delivery. Patching SG. Mol Neurobiol 54 1046-1077 (2017)
  10. Glucose Transporters in Cardiac Metabolism and Hypertrophy. Shao D, Tian R. Compr Physiol 6 331-351 (2015)
  11. A glimpse of structural biology through X-ray crystallography. Shi Y. Cell 159 995-1014 (2014)
  12. Elimination of substances from the brain parenchyma: efflux via perivascular pathways and via the blood-brain barrier. Hladky SB, Barrand MA. Fluids Barriers CNS 15 30 (2018)
  13. Glucose transporter GLUT1 expression and clinical outcome in solid tumors: a systematic review and meta-analysis. Wang J, Ye C, Chen C, Xiong H, Xie B, Zhou J, Chen Y, Zheng S, Wang L. Oncotarget 8 16875-16886 (2017)
  14. A guide to plasma membrane solute carrier proteins. Pizzagalli MD, Bensimon A, Superti-Furga G. FEBS J 288 2784-2835 (2021)
  15. Cell permeability beyond the rule of 5. Matsson P, Doak BC, Over B, Kihlberg J. Adv Drug Deliv Rev 101 42-61 (2016)
  16. Glut 1 in Cancer Cells and the Inhibitory Action of Resveratrol as A Potential Therapeutic Strategy. Zambrano A, Molt M, Uribe E, Salas M. Int J Mol Sci 20 E3374 (2019)
  17. Improving cellular uptake of therapeutic entities through interaction with components of cell membrane. Zhang R, Qin X, Kong F, Chen P, Pan G. Drug Deliv 26 328-342 (2019)
  18. Structure, mechanism and cooperation of bacterial multidrug transporters. Du D, van Veen HW, Murakami S, Pos KM, Luisi BF. Curr Opin Struct Biol 33 76-91 (2015)
  19. Cerebrospinal fluid biomarkers of neurovascular dysfunction in mild dementia and Alzheimer's disease. Sweeney MD, Sagare AP, Zlokovic BV. J Cereb Blood Flow Metab 35 1055-1068 (2015)
  20. Multidrug efflux pumps from Enterobacteriaceae, Vibrio cholerae and Staphylococcus aureus bacterial food pathogens. Andersen JL, He GX, Kakarla P, K C R, Kumar S, Lakra WS, Mukherjee MM, Ranaweera I, Shrestha U, Tran T, Varela MF. Int J Environ Res Public Health 12 1487-1547 (2015)
  21. Autophagy induction by trehalose: Molecular mechanisms and therapeutic impacts. Hosseinpour-Moghaddam K, Caraglia M, Sahebkar A. J Cell Physiol 233 6524-6543 (2018)
  22. An update on therapeutic opportunities offered by cancer glycolytic metabolism. Granchi C, Fancelli D, Minutolo F. Bioorg Med Chem Lett 24 4915-4925 (2014)
  23. The physiological role of drug transporters. Liang Y, Li S, Chen L. Protein Cell 6 334-350 (2015)
  24. Attacking the supply wagons to starve cancer cells to death. Selwan EM, Finicle BT, Kim SM, Edinger AL. FEBS Lett 590 885-907 (2016)
  25. Emerging role of N-myc downstream-regulated gene 2 (NDRG2) in cancer. Hu W, Fan C, Jiang P, Ma Z, Yan X, Di S, Jiang S, Li T, Cheng Y, Yang Y. Oncotarget 7 209-223 (2016)
  26. Nanoparticle-based targeted therapeutics in head-and-neck cancer. Wu TT, Zhou SH. Int J Med Sci 12 187-200 (2015)
  27. The proton-coupled folate transporter (PCFT-SLC46A1) and the syndrome of systemic and cerebral folate deficiency of infancy: Hereditary folate malabsorption. Zhao R, Aluri S, Goldman ID. Mol Aspects Med 53 57-72 (2017)
  28. A Glimpse of Membrane Transport through Structures-Advances in the Structural Biology of the GLUT Glucose Transporters. Yan N. J Mol Biol 429 2710-2725 (2017)
  29. The ins and outs of vesicular monoamine transporters. Yaffe D, Forrest LR, Schuldiner S. J Gen Physiol 150 671-682 (2018)
  30. Developments in Carbohydrate-Based Cancer Therapeutics. Hossain F, Andreana PR. Pharmaceuticals (Basel) 12 E84 (2019)
  31. Regulation of Amino Acid Transport in Saccharomyces cerevisiae. Bianchi F, Van't Klooster JS, Ruiz SJ, Poolman B. Microbiol Mol Biol Rev 83 e00024-19 (2019)
  32. Molecular Modeling of Drug-Transporter Interactions-An International Transporter Consortium Perspective. Schlessinger A, Welch MA, van Vlijmen H, Korzekwa K, Swaan PW, Matsson P. Clin Pharmacol Ther 104 818-835 (2018)
  33. A Historical Review of Brain Drug Delivery. Pardridge WM. Pharmaceutics 14 1283 (2022)
  34. Re-engineering therapeutic antibodies for Alzheimer's disease as blood-brain barrier penetrating bi-specific antibodies. Pardridge WM. Expert Opin Biol Ther 16 1455-1468 (2016)
  35. In silico pharmacology: Drug membrane partitioning and crossing. Di Meo F, Fabre G, Berka K, Ossman T, Chantemargue B, Paloncýová M, Marquet P, Otyepka M, Trouillas P. Pharmacol Res 111 471-486 (2016)
  36. Therapeutic Mechanisms of Herbal Medicines Against Insulin Resistance: A Review. Li J, Bai L, Wei F, Zhao J, Wang D, Xiao Y, Yan W, Wei J. Front Pharmacol 10 661 (2019)
  37. Pseudo Natural Products-Chemical Evolution of Natural Product Structure. Karageorgis G, Foley DJ, Laraia L, Brakmann S, Waldmann H. Angew Chem Int Ed Engl 60 15705-15723 (2021)
  38. Structure and function of thyroid hormone plasma membrane transporters. Schweizer U, Johannes J, Bayer D, Braun D. Eur Thyroid J 3 143-153 (2014)
  39. LncRNAs: The Regulator of Glucose and Lipid Metabolism in Tumor Cells. Lu W, Cao F, Wang S, Sheng X, Ma J. Front Oncol 9 1099 (2019)
  40. Development of Glucose Transporter (GLUT) Inhibitors. Reckzeh ES, Waldmann H. European J Org Chem 2020 2321-2329 (2020)
  41. Structure-Function Relationship of Transporters in the Glutamate-Glutamine Cycle of the Central Nervous System. Hayashi MK. Int J Mol Sci 19 E1177 (2018)
  42. Chemical biology probes of mammalian GLUT structure and function. Holman GD. Biochem J 475 3511-3534 (2018)
  43. Glucose transporters: cellular links to hyperglycemia in insulin resistance and diabetes. Stringer DM, Zahradka P, Taylor CG. Nutr Rev 73 140-154 (2015)
  44. Highlighting membrane protein structure and function: A celebration of the Protein Data Bank. Li F, Egea PF, Vecchio AJ, Asial I, Gupta M, Paulino J, Bajaj R, Dickinson MS, Ferguson-Miller S, Monk BC, Stroud RM. J Biol Chem 296 100557 (2021)
  45. The role of hypoxia in oral cancer and potentially malignant disorders: a review. Kujan O, Shearston K, Farah CS. J Oral Pathol Med 46 246-252 (2017)
  46. Understanding Conformational Dynamics of Complex Lipid Mixtures Relevant to Biology. Friedman R, Khalid S, Aponte-Santamaría C, Arutyunova E, Becker M, Boyd KJ, Christensen M, Coimbra JTS, Concilio S, Daday C, van Eerden FJ, Fernandes PA, Gräter F, Hakobyan D, Heuer A, Karathanou K, Keller F, Lemieux MJ, Marrink SJ, May ER, Mazumdar A, Naftalin R, Pickholz M, Piotto S, Pohl P, Quinn P, Ramos MJ, Schiøtt B, Sengupta D, Sessa L, Vanni S, Zeppelin T, Zoni V, Bondar AN, Domene C. J Membr Biol 251 609-631 (2018)
  47. "Just a spoonful of sugar...": import of sialic acid across bacterial cell membranes. North RA, Horne CR, Davies JS, Remus DM, Muscroft-Taylor AC, Goyal P, Wahlgren WY, Ramaswamy S, Friemann R, Dobson RCJ. Biophys Rev 10 219-227 (2018)
  48. An Overview of Cell-Based Assay Platforms for the Solute Carrier Family of Transporters. Dvorak V, Wiedmer T, Ingles-Prieto A, Altermatt P, Batoulis H, Bärenz F, Bender E, Digles D, Dürrenberger F, Heitman LH, IJzerman AP, Kell DB, Kickinger S, Körzö D, Leippe P, Licher T, Manolova V, Rizzetto R, Sassone F, Scarabottolo L, Schlessinger A, Schneider V, Sijben HJ, Steck AL, Sundström H, Tremolada S, Wilhelm M, Wright Muelas M, Zindel D, Steppan CM, Superti-Furga G. Front Pharmacol 12 722889 (2021)
  49. Glucose transportation in the brain and its impairment in Huntington disease: one more shade of the energetic metabolism failure? Morea V, Bidollari E, Colotti G, Fiorillo A, Rosati J, De Filippis L, Squitieri F, Ilari A. Amino Acids 49 1147-1157 (2017)
  50. Implications of Resveratrol on Glucose Uptake and Metabolism. León D, Uribe E, Zambrano A, Salas M. Molecules 22 E398 (2017)
  51. Mycobacterium tuberculosis Major Facilitator Superfamily Transporters. Li P, Gu Y, Li J, Xie L, Li X, Xie J. J Membr Biol 250 573-585 (2017)
  52. Molecular Tools for Facilitative Carbohydrate Transporters (Gluts). Tanasova M, Fedie JR. Chembiochem 18 1774-1788 (2017)
  53. Toward a Molecular Basis of Cellular Nucleoside Transport in Humans. Wright NJ, Lee SY. Chem Rev 121 5336-5358 (2021)
  54. Surface Modification of Iron Oxide-Based Magnetic Nanoparticles for Cerebral Theranostics: Application and Prospection. Wu Y, Lu Z, Li Y, Yang J, Zhang X. Nanomaterials (Basel) 10 E1441 (2020)
  55. Avian and Mammalian Facilitative Glucose Transporters. Byers MS, Howard C, Wang X. Microarrays (Basel) 6 E7 (2017)
  56. Melatonin Uptake by Cells: An Answer to Its Relationship with Glucose? Mayo JC, Aguado A, Cernuda-Cernuda R, Álvarez-Artime A, Cepas V, Quirós-González I, Hevia D, Sáinz RM. Molecules 23 E1999 (2018)
  57. More Than Meets the Eye Regarding Cancer Metabolism. Kubicka A, Matczak K, Łabieniec-Watała M. Int J Mol Sci 22 9507 (2021)
  58. Strategic Moves of "Superbugs" Against Available Chemical Scaffolds: Signaling, Regulation, and Challenges. Baral B, Mozafari MR. ACS Pharmacol Transl Sci 3 373-400 (2020)
  59. Endocytosis of nutrient transporters in fungi: The ART of connecting signaling and trafficking. Barata-Antunes C, Alves R, Talaia G, Casal M, Gerós H, Mans R, Paiva S. Comput Struct Biotechnol J 19 1713-1737 (2021)
  60. G Protein-Coupled Receptors in the Mammalian Blood-Brain Barrier. Pluimer BR, Colt M, Zhao Z. Front Cell Neurosci 14 139 (2020)
  61. Regulatory Mechanisms of LncRNAs in Cancer Glycolysis: Facts and Perspectives. Huang P, Zhu S, Liang X, Zhang Q, Luo X, Liu C, Song L. Cancer Manag Res 13 5317-5336 (2021)
  62. Antiviral Activity of Carrageenans and Processing Implications. Álvarez-Viñas M, Souto S, Flórez-Fernández N, Torres MD, Bandín I, Domínguez H. Mar Drugs 19 437 (2021)
  63. Erythroid glucose transport in health and disease. Guizouarn H, Allegrini B. Pflugers Arch 472 1371-1383 (2020)
  64. The role of SLC transporters for brain health and disease. Nguyen YTK, Ha HTT, Nguyen TH, Nguyen LN. Cell Mol Life Sci 79 20 (2021)
  65. Mapping the multiscale structure of biological systems. Schaffer LV, Ideker T. Cell Syst 12 622-635 (2021)
  66. Mechanistic Insights into Protein Stability and Self-aggregation in GLUT1 Genetic Variants Causing GLUT1-Deficiency Syndrome. Raja M, Kinne RKH. J Membr Biol 253 87-99 (2020)
  67. N-myc Downstream-Regulated Gene 2 (NDRG2) Function as a Positive Regulator of Apoptosis: A New Insight into NDRG2 as a Tumor Suppressor. Kim G, Lim S, Kim KD. Cells 10 2649 (2021)
  68. Transporter oligomerisation: roles in structure and function. Cecchetti C, Pyle E, Byrne B. Biochem Soc Trans 47 433-440 (2019)
  69. Hepatic drug transporters: the journey so far. Riley RJ, Foley SA, Barton P, Soars MG, Williamson B. Expert Opin Drug Metab Toxicol 12 201-216 (2016)
  70. Glycoconjugation: An approach to cancer therapeutics. Molejon MI, Weiz G, Breccia JD, Vaccaro MI. World J Clin Oncol 11 110-120 (2020)
  71. Membrane Protein Stabilization Strategies for Structural and Functional Studies. Errasti-Murugarren E, Bartoccioni P, Palacín M. Membranes (Basel) 11 155 (2021)
  72. The Major Facilitator Superfamily and Antimicrobial Resistance Efflux Pumps of the ESKAPEE Pathogen Staphylococcus aureus. Stephen J, Salam F, Lekshmi M, Kumar SH, Varela MF. Antibiotics (Basel) 12 343 (2023)
  73. The Structure and Function of OxlT, the Oxalate Transporter of Oxalobacter formigenes. Iyalomhe O, Khantwal CM, Kang DC. J Membr Biol 248 641-650 (2015)
  74. The evolving biology of the proton-coupled folate transporter: New insights into regulation, structure, and mechanism. Hou Z, Gangjee A, Matherly LH. FASEB J 36 e22164 (2022)
  75. Hemiplegic Migraine in Glut1 Deficiency Syndrome and Paroxysmal Dyskinesia at Ketogenic Diet Induction: Case Report and Literature Review. Gburek-Augustat J, Heinze A, Abou Jamra R, Merkenschlager A. Mov Disord Clin Pract 7 965-970 (2020)
  76. L-Glucose: Another Path to Cancer Cells. Ono K, Takigawa S, Yamada K. Cancers (Basel) 12 E850 (2020)
  77. An appraisal of the current status of inhibition of glucose transporters as an emerging antineoplastic approach: Promising potential of new pan-GLUT inhibitors. Temre MK, Kumar A, Singh SM. Front Pharmacol 13 1035510 (2022)
  78. Discovery and Development of Inhibitors of the Plasmodial FNT-Type Lactate Transporter as Novel Antimalarials. Nerlich C, Epalle NH, Seick P, Beitz E. Pharmaceuticals (Basel) 14 1191 (2021)
  79. Natural Products and Derivatives Targeting at Cancer Energy Metabolism: A Potential Treatment Strategy. Wang QQ, Li MX, Li C, Gu XX, Zheng MZ, Chen LX, Li H. Curr Med Sci 40 205-217 (2020)
  80. Toward a Systematic Structural and Functional Annotation of Solute Carriers Transporters-Example of the SLC6 and SLC7 Families. Colas C. Front Pharmacol 11 1229 (2020)
  81. ABCB1 and ABCG2 Regulation at the Blood-Brain Barrier: Potential New Targets to Improve Brain Drug Delivery. Schulz JA, Hartz AMS, Bauer B. Pharmacol Rev 75 815-853 (2023)
  82. Obesity and Type 2 Diabetes Mellitus Explained by the Free Energy Principle. Peters A, Hartwig M, Spiller T. Front Psychol 13 931701 (2022)
  83. One Molecule for Mental Nourishment and More: Glucose Transporter Type 1-Biology and Deficiency Syndrome. Vulturar R, Chiș A, Pintilie S, Farcaș IM, Botezatu A, Login CC, Sitar-Taut AV, Orasan OH, Stan A, Lazea C, Al-Khzouz C, Mager M, Vințan MA, Manole S, Damian L. Biomedicines 10 1249 (2022)
  84. A Glimpse into Milestones of Insulin Resistance and an Updated Review of Its Management. Aedh AI, Alshahrani MS, Huneif MA, Pryme IF, Oruch R. Nutrients 15 921 (2023)
  85. Diverse Roles of Protein Palmitoylation in Cancer Progression, Immunity, Stemness, and Beyond. Li M, Zhang L, Chen CW. Cells 12 2209 (2023)
  86. How Cryo-EM Has Expanded Our Understanding of Membrane Transporters. Baril SA, Gose T, Schuetz JD. Drug Metab Dispos 51 904-922 (2023)
  87. Non-viral approaches for gene therapy and therapeutic genome editing across the blood-brain barrier. Xie R, Wang Y, Burger JC, Li D, Zhu M, Gong S. Med X 1 6 (2023)
  88. Targeting SLC transporters: small molecules as modulators and therapeutic opportunities. Schlessinger A, Zatorski N, Hutchinson K, Colas C. Trends Biochem Sci 48 801-814 (2023)
  89. [Regulation of tumor cell glycometabolism and tumor therapy]. Liu G, Song G. Sheng Wu Yi Xue Gong Cheng Xue Za Zhi 36 691-695 (2019)

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