Cryo-electron microscopy structure of a zinc uptake ABC transporter
Changxu Pang1, Hoang Nguyen2,3, Qingfang Zhang2
1Biology Department, Brookhaven National Laboratory; Upton, NY 11973, USA.
Biorxiv : the Preprint Server for Biology
|July 9, 2025
Summary
Bacteria use high-affinity zinc transporters (ABC transporters) to scavenge scarce zinc. This study reveals how the Escherichia coli ZnuB-ZnuC transporter structure changes to control zinc uptake, offering new pathogen targets.
Area of Science:
- Microbiology
- Structural Biology
- Biochemistry
Background:
- Bacteria require zinc (Zn2+) for essential cellular functions.
- High-affinity ABC transporters are crucial for bacterial zinc acquisition.
- The structures and regulatory mechanisms of these transporters remain largely unknown.
Purpose of the Study:
- To elucidate the structure of the *Escherichia coli* ZnuB-ZnuC zinc transporter complex.
- To understand the molecular mechanisms governing bacterial zinc uptake and regulation.
Main Methods:
- Cryo-electron microscopy (cryo-EM) was used to determine the structure of the ZnuB-ZnuC complex.
- Structural analysis focused on the conformation, cavity, and domain organization of the transporter.
Main Results:
- Cryo-EM structures revealed a ZnuB homodimer in an outward-facing, sealed conformation.
- The ZnuC subunit comprises an ATP-binding cassette and a zinc-sensing domain (ZSD).
- Zn2+ binding to the ZSD inhibits the transporter, while ZSD disorder enables uptake under low-zinc conditions.
Conclusions:
- The study clarifies the molecular basis of bacterial zinc acquisition via the ZnuB-ZnuC transporter.
- The findings reveal a novel regulatory mechanism involving the ZSD and zinc availability.
- This work identifies potential new targets for disrupting metal homeostasis in pathogenic bacteria.
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