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