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- Title
Crystal structure of human sex hormone-binding globulin: steroid transport by a laminin G-like domain.
- Authors
Grishkovskaya, Irina; Avvakumov, George V.; Sklenar, Gisela; Dales, David; Hammond, Geoffrey L.; Muller, Yves A.
- Abstract
Human sex hormone-binding globulin (SHRG) 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 5α-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 Β-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.
- Subjects
SEX hormones; GLOBULINS; BLOOD proteins; STEROID-binding proteins; GLYCOPROTEINS; BIOCHEMISTRY
- Publication
EMBO Journal, 2000, Vol 19, Issue 4, p504
- ISSN
0261-4189
- Publication type
Article
- DOI
10.1093/emboj/19.4.504