| Autor: |
Grishkovskaya, Irina, Avvakumov, George V., Sklenar, Gisela, Dales, David, Hammond, Geoffrey L., Muller, Yves A. |
| Předmět: |
|
| Zdroj: |
EMBO Journal; 2/15/2000, Vol. 19 Issue 4, p504-512, 9p |
| Abstrakt: |
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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
|
Plný text