RT Journal Article
SR Electronic
T1 Molecular insights into substrate translocation in an elevator-type metal transporter
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2024.09.18.613805
DO 10.1101/2024.09.18.613805
A1 Zhang, Yao
A1 Jafari, Majid
A1 Zhang, Tuo
A1 Sui, Dexin
A1 Sagresti, Luca
A1 Merz, Kenneth M.
A1 Hu, Jian
YR 2024
UL http://biorxiv.org/content/early/2024/09/19/2024.09.18.613805.abstract
AB The Zrt/Irt-like protein (ZIP) metal transporters are key players in maintaining the homeostasis of a panel of essential microelements. The prototypical ZIP from Bordetella bronchiseptica (BbZIP) is an elevator transporter, but how the metal substrate moves along the transport pathway and how the transporter changes conformation to allow alternating access remain to be elucidated. Here, we combined structural, biochemical, and computational approaches to investigate the process of metal substrate translocation along with the global structural rearrangement. Our study revealed an upward hinge motion of the transport domain in a high-resolution crystal structure of a cross-linked variant, elucidated the mechanisms of metal release from the transport site into the cytoplasm and activity regulation by a cytoplasmic metal-binding loop, and unraveled an unusual elevator mode in enhanced sampling simulations that distinguishes BbZIP from other elevator transporters. This work provides important insights into the metal transport mechanism of the ZIP family.Competing Interest StatementThe authors have declared no competing interest.