High-resolution structure of a mercury cross-linked ZIP metal transporter reveals delicate motions and metal relay for regulated zinc transport.

ABSTRACT: Zrt-/Irt-like protein (ZIP) divalent metal transporters play a central role in maintaining trace element homeostasis. The prototypical ZIP from Bordetella bronchiseptica (BbZIP) is an elevator-type transporter, but the dynamic motions and detailed transport mechanism remain to be elucidated. Here, we report a high-resolution crystal structure of a mercury-crosslinked BbZIP variant at 1.95 Å, revealing an upward rotation of the transport domain in the new inward-facing conformation and a water-filled metal release channel that is divided into two parallel pathways by the previously disordered cytoplasmic loop. Mutagenesis and transport assays indicated that the newly identified high-affinity metal binding site in the primary pathway acts as a "metal sink" to reduce the transport rate

SUBMITTER: Zhang T 

PROVIDER: S-EPMC10153219 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature