The HDQVH-motif in domain E of the estradiol receptor alpha is responsible for zinc-binding and zinc-induced hormone release.

摘要

The estradiol receptor alpha and proteolytic fragments thereof which contain the entire ligand-binding domain E, bind 65Zn with high affinity. Four putative double-histidine zinc-binding sequences can be identified within the hormone-binding domain E: HDQVH [amino acid (aa) 373-377], HIH (aa 474-476), HFRH (aa 513-516) and HRLH (aa 547-550). Only the HDQVH-motif is responsible for the 1:1 zinc-binding to domain E because the proteolytic (endo-Lys-C) 17 kDa fragment (aa 303-467) from porcine estradiol receptor alpha possesses the zinc-binding ability but none of the fragments containing the other motifs. In addition, H373A- and H377A-mutants lack the metal-binding capacity. Moreover, divalent metal ions are able to release estradiol out of the binding-niche. The order for this feature parallels the competition pattern of 65Zn-binding: Mg2+ < Ni2+ < Zn2+ < or = Cu2+. Mutant estradiol receptor alpha fragments (H373A and H377A) lack the zinc-induced hormone release.