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Crystal structure of human sex hormone-binding globulin: steroid transport by a laminin G-like domain.

Grishkovskaya I, Avvakumov GV, Sklenar G, Dales D, Hammond GL, Muller YA
EMBO J 19 504-12 (2000)
Cited: 97 times
EuropePMC logo PMID: 10675319

Abstract

Human sex hormone-binding globulin (SHBG) transports sex steroids in blood and regulates their access to target tissues. In biological fluids, SHBG exists as a homodimer and each monomer comprises two laminin G-like domains (G domains). The crystal structure of the N-terminal G domain of SHBG in complex with 5alpha-dihydrotestosterone at 1.55 A resolution reveals both the architecture of the steroid-binding site and the quaternary structure of the dimer. We also show that G domains have jellyroll topology and are structurally related to pentraxin. In each SHBG monomer, the steroid intercalates into a hydrophobic pocket within the beta-sheet sandwich. The steroid and a 20 A distant calcium ion are not located at the dimer interface. Instead, two separate steroid-binding pockets and calcium-binding sites exist per dimer. The structure displays intriguing disorder for loop segment Pro130-Arg135. In all other jellyroll proteins, this loop is well ordered. If modelled accordingly, it covers the steroid-binding site and could thereby regulate access of ligands to the binding pocket.

Articles - 1d2s mentioned but not cited (21)

  1. Crystal structure of human sex hormone-binding globulin: steroid transport by a laminin G-like domain. Grishkovskaya I, Avvakumov GV, Sklenar G, Dales D, Hammond GL, Muller YA. EMBO J 19 504-512 (2000)
  2. Investigation of atomic level patterns in protein--small ligand interactions. Chen K, Kurgan L. PLoS One 4 e4473 (2009)
  3. Endocrine Disruption: Computational Perspectives on Human Sex Hormone-Binding Globulin and Phthalate Plasticizers. Sheikh IA, Turki RF, Abuzenadah AM, Damanhouri GA, Beg MA. PLoS One 11 e0151444 (2016)
  4. Structural model of the amino propeptide of collagen XI alpha1 chain with similarity to the LNS domains. Fallahi A, Kroll B, Warner LR, Oxford RJ, Irwin KM, Mercer LM, Shadle SE, Oxford JT. Protein Sci 14 1526-1537 (2005)
  5. Analysis of the "thermodynamic information content" of a Homo sapiens structural database reveals hierarchical thermodynamic organization. Larson SA, Hilser VJ. Protein Sci 13 1787-1801 (2004)
  6. Genetics of PCOS: A systematic bioinformatics approach to unveil the proteins responsible for PCOS. Panda PK, Rane R, Ravichandran R, Singh S, Panchal H. Genom Data 8 52-60 (2016)
  7. Human sex hormone-binding globulin as a potential target of alternate plasticizers: an in silico study. Sheikh IA, Yasir M, Abu-Elmagd M, Dar TA, Abuzenadah AM, Damanhouri GA, Al-Qahtani M, Beg MA. BMC Struct Biol 16 15 (2016)
  8. Molecular interactions between sex hormone-binding globulin and nonsteroidal ligands that enhance androgen activity. Round P, Das S, Wu TS, Wähälä K, Van Petegem F, Hammond GL. J Biol Chem 295 1202-1211 (2020)
  9. Unleashing the power of meta-threading for evolution/structure-based function inference of proteins. Brylinski M. Front Genet 4 118 (2013)
  10. Modulating testosterone pathway: a new strategy to tackle male skin aging? Bernard P, Scior T, Do QT. Clin Interv Aging 7 351-361 (2012)
  11. Quantitative surface field analysis: learning causal models to predict ligand binding affinity and pose. Cleves AE, Jain AN. J Comput Aided Mol Des 32 731-757 (2018)
  12. Arginine-140 and isoleucine-141 determine the 17beta-estradiol-binding specificity of the sex-steroid-binding protein (SBP, or SHBG) of human plasma. Petra PH, Adman ET, Orr WR, Woodcock KT, Groff C, Sui LM. Protein Sci 10 1811-1821 (2001)
  13. SHBG141-161 Domain-Peptide Stimulates GPRC6A-Mediated Response in Leydig and β-Langerhans cell lines. De Toni L, Guidolin D, De Filippis V, Peterle D, Rocca MS, Di Nisio A, De Rocco Ponce M, Foresta C. Sci Rep 9 19432 (2019)
  14. Creation of a free, Internet-accessible database: the Multiple Target Ligand Database. Chen C, He Y, Wu J, Zhou J. J Cheminform 7 14 (2015)
  15. Exploiting Blood Transport Proteins as Carborane Supramolecular Vehicles for Boron Neutron Capture Therapy. Marforio TD, Mattioli EJ, Zerbetto F, Calvaresi M. Nanomaterials (Basel) 13 1770 (2023)
  16. Potency of Hexaconazole to Disrupt Endocrine Function with Sex Hormone-Binding Globulin. Alquraini A. Int J Mol Sci 24 3882 (2023)
  17. Potential Disruption of Systemic Hormone Transport by Tobacco Alkaloids Using Computational Approaches. Rehan M, Zargar UR, Sheikh IA, Alharthy SA, Almashjary MN, Abuzenadah AM, Beg MA. Toxics 10 727 (2022)
  18. The dipeptidyl peptidase IV inhibitors vildagliptin and K-579 inhibit a phospholipase C: a case of promiscuous scaffolds in proteins. Chakraborty S, Rendón-Ramírez A, Ásgeirsson B, Dutta M, Ghosh AS, Oda M, Venkatramani R, Rao BJ, Dandekar AM, Goñi FM. F1000Res 2 286 (2013)
  19. Characterization and comparison of recombinant full-length ursine and human sex hormone-binding globulin. Frøbert AM, Brohus M, Toews JNC, Round P, Fröbert O, Hammond GL, Overgaard MT. FEBS Open Bio 12 362-378 (2022)
  20. HyperBeta: characterizing the structural dynamics of proteins and self-assembling peptides. Nobile MS, Fontana F, Manzoni L, Cazzaniga P, Mauri G, Saracino GAA, Besozzi D, Gelain F. Sci Rep 11 7783 (2021)
  21. Not Drug-like, but Like Drugs: Cnidaria Natural Products. Laguionie-Marchais C, Allcock AL, Baker BJ, Conneely EA, Dietrick SG, Kearns F, McKeever K, Young RM, Sierra CA, Soldatou S, Woodcock HL, Johnson MP. Mar Drugs 20 42 (2021)


Reviews citing this publication (24)

  1. Steroid-hormone rapid actions, membrane receptors and a conformational ensemble model. Norman AW, Mizwicki MT, Norman DP. Nat Rev Drug Discov 3 27-41 (2004)
  2. Structure and function of laminin LG modules. Timpl R, Tisi D, Talts JF, Andac Z, Sasaki T, Hohenester E. Matrix Biol 19 309-317 (2000)
  3. Diverse roles for sex hormone-binding globulin in reproduction. Hammond GL. Biol Reprod 85 431-441 (2011)
  4. Plasma steroid-binding proteins: primary gatekeepers of steroid hormone action. Hammond GL. J Endocrinol 230 R13-25 (2016)
  5. A Reappraisal of Testosterone's Binding in Circulation: Physiological and Clinical Implications. Goldman AL, Bhasin S, Wu FCW, Krishna M, Matsumoto AM, Jasuja R. Endocr Rev 38 302-324 (2017)
  6. Neurosteroid binding sites on GABA(A) receptors. Hosie AM, Wilkins ME, Smart TG. Pharmacol Ther 116 7-19 (2007)
  7. Domain structure and organisation in extracellular matrix proteins. Hohenester E, Engel J. Matrix Biol 21 115-128 (2002)
  8. Rapid actions of androgens. Michels G, Hoppe UC. Front Neuroendocrinol 29 182-198 (2008)
  9. The role of female hormones on lung function in chronic lung diseases. Tam A, Morrish D, Wadsworth S, Dorscheid D, Man SF, Sin DD. BMC Womens Health 11 24 (2011)
  10. Structural and functional diversity generated by alternative mRNA splicing. Stetefeld J, Ruegg MA. Trends Biochem Sci 30 515-521 (2005)
  11. Sex hormone-binding globulin and type 2 diabetes mellitus. Le TN, Nestler JE, Strauss JF, Wickham EP. Trends Endocrinol Metab 23 32-40 (2012)
  12. Sex hormone-binding globulin gene expression in the liver: drugs and the metabolic syndrome. Pugeat M, Nader N, Hogeveen K, Raverot G, Déchaud H, Grenot C. Mol Cell Endocrinol 316 53-59 (2010)
  13. LG/LNS domains: multiple functions -- one business end? Rudenko G, Hohenester E, Muller YA. Trends Biochem Sci 26 363-368 (2001)
  14. Structural analyses of sex hormone-binding globulin reveal novel ligands and function. Avvakumov GV, Cherkasov A, Muller YA, Hammond GL. Mol Cell Endocrinol 316 13-23 (2010)
  15. Sex Hormone-Binding Globulin (SHBG), estradiol and breast cancer. Fortunati N, Catalano MG, Boccuzzi G, Frairia R. Mol Cell Endocrinol 316 86-92 (2010)
  16. Access of reproductive steroids to target tissues. Hammond GL. Obstet Gynecol Clin North Am 29 411-423 (2002)
  17. Sex hormone-binding globulin genetic variation: associations with type 2 diabetes mellitus and polycystic ovary syndrome. Chen C, Smothers J, Lange A, Nestler JE, Strauss Iii JF, Wickham Iii EP. Minerva Endocrinol 35 271-280 (2010)
  18. Studies of metabolite-protein interactions: a review. Matsuda R, Bi C, Anguizola J, Sobansky M, Rodriguez E, Vargas Badilla J, Zheng X, Hage B, Hage DS. J Chromatogr B Analyt Technol Biomed Life Sci 966 48-58 (2014)
  19. Preclinical profiles of progestins used in formulations of oral contraceptives and hormone replacement therapy. Hammond GL, Rabe T, Wagner JD. Am J Obstet Gynecol 185 S24-31 (2001)
  20. Role of sex hormone-binding globulin in the free hormone hypothesis and the relevance of free testosterone in androgen physiology. Narinx N, David K, Walravens J, Vermeersch P, Claessens F, Fiers T, Lapauw B, Antonio L, Vanderschueren D. Cell Mol Life Sci 79 543 (2022)
  21. Anabolic-androgenic steroids: How do they work and what are the risks? Bond P, Smit DL, de Ronde W. Front Endocrinol (Lausanne) 13 1059473 (2022)
  22. Structure/function analyses of human sex hormone-binding globulin: effects of zinc on steroid-binding specificity. Hammond GL, Avvakumov GV, Muller YA. J Steroid Biochem Mol Biol 85 195-200 (2003)
  23. Testosterone Retention Mechanism in Sertoli Cells: A Biochemical Perspective. Gill-Sharma MK. Open Biochem J 12 103-112 (2018)
  24. SHBG and Insulin resistance - Nexus revisited. Dinakaran A, Ar S, Rajagambeeram R, Nanda SK, Daniel M. Bioinformation 20 816-821 (2024)

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