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| The EMBO Journal
(2000) 19, 504–512, doi:10.1093/emboj/19.4.504 |
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| Crystal structure of human sex hormone-binding globulin: steroid transport by a laminin G-like domain |
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| Irina Grishkovskaya1, George V. Avvakumov2, Gisela Sklenar1, David Dales2, Geoffrey L. Hammond2 and Yves A. Muller1 |
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1 Forschungsgruppe Kristallographie, Max-Delbrück-Center for Molecular Medicine, Robert-Roessle-Strasse 10, D-13092 Berlin, Germany 2 Departments of Obstetrics & Gynaecology and Pharmacology & Toxicology, MRC Group in Fetal and Neonatal Health and Development, University of Western Ontario, London, Ontario N6A 4L6, Canada To whom correspondence should be addressed Yves A. Muller, yam@mdc-berlin.de Received 21 October 1999; Revised 10 December 1999; Accepted 10 December 1999. |
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| Abstract |
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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 5 -dihydrotestosterone at 1.55 Å 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  -sheet sandwich. The steroid and a 20 Å 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. |
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| Keywords: calcium binding, dimerization, jellyroll fold, plasma protein, sex steroids |
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