Abstract:
: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 Cd(2+), Co(2+) or Zn(2+) 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. Taken together, these findings elucidate a previously unknown MBD and suggest new regulatory mechanisms for metal transport by P1B-ATPases.
journal_name
Nat Chem Bioljournal_title
Nature chemical biologyauthors
Smith AT,Barupala D,Stemmler TL,Rosenzweig ACdoi
10.1038/nchembio.1863subject
Has Abstractpub_date
2015-09-01 00:00:00pages
678-84issue
9eissn
1552-4450issn
1552-4469pii
nchembio.1863journal_volume
11pub_type
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