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

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Item Type:	Article
Title:	Crystal structure of human sex hormone-binding globulin: steroid transport by a laminin G-like domain
Creators Name:	Grishkovskaya, I., Avvakumov, G.V., Sklenar, G., Dales, D., Hammond, G.L. and Muller, Y.A.
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 5α-dihydrotestosterone at 1.55 {angstrom} 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 {angstrom} 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.
Keywords:	Calcium Binding, Dimerization, Jellyroll Fold, Plasma Protein, Sex Steroids, Animals, Rats
Source:	EMBO Journal
ISSN:	0261-4189
Publisher:	Oxford University Press
Volume:	19
Number:	4
Page Range:	504-512
Date:	15 February 2000
PubMed:	View item in PubMed

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