biostudies-literatureZhang YNIAID NIH HHSU.S. Department of Health & Human Services | NIH | Center for Information TechnologyNIGMS NIH HHSU.S. Department of Health & Human Services | National Institutes of Health385https://www.ebi.ac.uk/biostudies/studies/S-EPMC9873690biostudies-literatureUnknown14(1)The Zrt-/Irt-like protein (ZIP) family consists of ubiquitously expressed divalent metal transporters critically involved in maintaining systemic and cellular homeostasis of zinc, iron, and manganese. Here, we present a study on a prokaryotic ZIP from Bordetella bronchiseptica (BbZIP) by combining structural biology, evolutionary covariance, computational modeling, and a variety of biochemical assays to tackle the issue of the transport mechanism which has not been established for the ZIP family. The apo state structure in an inward-facing conformation revealed a disassembled transport site, altered inter-helical interactions, and importantly, a rigid body movement of a 4-transmembrane helix (TM) bundle relative to the other TMs. The computationally generated and biochemically validated outward-facing conformation model revealed a slide of the 4-TM bundle, which carries the transport site(s), by approximately 8 Å toward the extracellular side against the static TMs which mediate dimerization. These findings allow us to conclude that BbZIP is an elevator-type transporter.Nature communicationsStructural insights into the elevator-type transport mechanism of a bacterial ZIP metal transporter.PMC9873690R35 GM140931GM140931GM129004GM126189AI164266R01 GM126189R01 GM129004R01 AI164266Jiang YWei GWSui DHu JZhang YGao KYu PSu MfalseStructural insights into the elevator-type transport mechanism of a bacterial ZIP metal transporter.The Zrt-/Irt-like protein (ZIP) family consists of ubiquitously expressed divalent metal transporters critically involved in maintaining systemic and cellular homeostasis of zinc, iron, and manganese. Here, we present a study on a prokaryotic ZIP from Bordetella bronchiseptica (BbZIP) by combining structural biology, evolutionary covariance, computational modeling, and a variety of biochemical assays to tackle the issue of the transport mechanism which has not been established for the ZIP family. The apo state structure in an inward-facing conformation revealed a disassembled transport site, altered inter-helical interactions, and importantly, a rigid body movement of a 4-transmembrane helix (TM) bundle relative to the other TMs. The computationally generated and biochemically validated outward-facing conformation model revealed a slide of the 4-TM bundle, which carries the transport site(s), by approximately 8 Å toward the extracellular side against the static TMs which mediate dimerization. These findings allow us to conclude that BbZIP is an elevator-type transporter.2023-01-01T00:00:00Z2023 Jan2026-05-10T06:58:12.579Z2025-04-05T20:20:35.6ZS-EPMC98736903669384310.1038/s41467-023-36048-4