1D2S

CRYSTAL STRUCTURE OF THE N-TERMINAL LAMININ G-LIKE DOMAIN OF SHBG IN COMPLEX WITH DIHYDROTESTOSTERONE

Summary for 1D2S

• Entry DOI: 10.2210/pdb1d2s/pdb
• Descriptor: SEX HORMONE-BINDING GLOBULIN, CALCIUM ION, 5-ALPHA-DIHYDROTESTOSTERONE, ... (4 entities in total)
• Functional Keywords: steroid transport, laminin g-like domain, jellyroll, androgen binding protein (abp), sex steroid binding protein (sbp), transport protein
• Biological source: Homo sapiens (human)
• Cellular location: Secreted : P04278
• Total number of polymer chains: 1
• Total formula weight: 19226.01

Authors

Grishkovskaya, I.,Avvakumov, G.V.,Sklenar, G.,Dales, D.,Hammond, G.L.,Muller, Y.A. (deposition date: 1999-09-28, release date: 2000-06-28, Last modification date: 2024-10-30)

Primary citation

Grishkovskaya, I.,Avvakumov, G.V.,Sklenar, G.,Dales, D.,Hammond, G.L.,Muller, Y.A.
Crystal structure of human sex hormone-binding globulin: steroid transport by a laminin G-like domain.
EMBO J., 19:504-512, 2000

PubMed 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.

PubMed: 10675319
DOI: 10.1093/emboj/19.4.504

Experimental method

X-RAY DIFFRACTION (1.55 Å)