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

Human sex hormone-binding globulin (SHBG) transports sex steroids in blood and regulates their access to target tissues. In biological fluids, SHBG ex ists 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 com plex with 5 alpha-dihydrotestosterone at 1.55 Angstrom resolution reveals b oth the architecture of the steroid-binding site and the quaternary structu re of the dimer, We also show that G domains have jellyroll topology and ar e structurally related to pentraxin. In each SHBG monomer, the steroid inte rcalates into a hydrophobic pocket within the beta-sheet sandwich. The ster oid and a 20 Angstrom distant calcium ion are not located at the dimer inte rface. Instead, two separate steroid-binding pockets and calcium-binding si tes exist per dimer, The structure displays intriguing disorder for loop se gment Pro130-Arg135. In all other jellyroll proteins, this loop is well ord ered. If modelled accordingly, it covers the steroid-binding site and could thereby regulate access of ligands to the binding pocket.