Asymmetric functions of a binuclear metal center within the transport pathway of a human zinc transporter ZIP4.

ABSTRACT: Metal clusters are exploited by numerous metalloenzymes for catalysis, but it is not common to utilize a metal cluster for substrate transport across membrane. The recent crystal structure of a prototypic Zrt-/Irt-like protein (ZIP) metal transporter from Bordetella bronchiseptica (BbZIP) revealed an unprecedented binuclear metal center (BMC) within the transport pathway. Here, through a combination of bioinformatics, biochemical and structural approaches, we concluded that the two physically associated metal-binding sites in the BMC of human ZIP4 (hZIP4) zinc transporter exert different functions: one conserved transition metal-binding site acts as the transport site essential for activity, whereas the variable metal-binding site is required for hZIP4's optimal activity presumably by serv

SUBMITTER: Zhang T 

PROVIDER: S-EPMC6956730 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature