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Title: A New Metal Binding Domain Involved in Cadmium, Cobalt and Zinc Transport

Journal Article · · Nature Chemical Biology
 [1];  [2];  [2];  [1]
  1. Northwestern Univ., Evanston, IL (United States)
  2. Wayne State Univ., Detroit, MI (United States)

In the P1B-ATPases, which couple cation transport across membranes to ATP hydrolysis, are central to metal homeostasis in all organisms. An important feature of P1B-ATPases is the presence of soluble metal binding domains (MBDs) that regulate transport activity. Only one type of MBD has been characterized extensively, but bioinformatics analyses indicate that a diversity of MBDs may exist in nature. Here we report the biochemical, structural and functional characterization of a new MBD from the Cupriavidus metallidurans P1B-4-ATPase CzcP (CzcP MBD). The CzcP MBD binds two Cd2+, Co2+ or Zn2+ ions in distinct and unique sites and adopts an unexpected fold consisting of two fused ferredoxin-like domains. Both in vitro and in vivo activity assays using full-length CzcP, truncated CzcP and several variants indicate a regulatory role for the MBD and distinct functions for the two metal binding sites. Moreover, these findings elucidate a previously unknown MBD and suggest new regulatory mechanisms for metal transport by P1B-ATPases.

Research Organization:
Brookhaven National Laboratory (BNL), Upton, NY (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Basic Energy Sciences (BES)
DOE Contract Number:
SC00112704
OSTI ID:
1228887
Report Number(s):
BNL-110962-2015-JA
Journal Information:
Nature Chemical Biology, Vol. 11; ISSN 1552-4450
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
English

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Unique roles of iron and zinc binding to the yeast Fe–S cluster scaffold assembly protein “Isu1” journal January 2019
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Characterization of the heavy metal binding properties of periplasmic metal uptake protein CLas-ZnuA2 journal January 2020
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