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Metal binding protein PDB id
2klt
Jmol
Contents
Protein chain
156 a.a. *
* Residue conservation analysis
PDB id:
2klt
Name: Metal binding protein
Title: Second ca2+ binding domain of ncx1.3
Structure: Sodium/calcium exchanger 1. Chain: a. Fragment: second ca2+ binding domain. Synonym: na(+)/ca(2+)-exchange protein 1. Engineered: yes
Source: Canis familiaris. Dog. Organism_taxid: 9615. Gene: slc8a1. Expressed in: escherichia coli. Expression_system_taxid: 562. Expression_system_variant: de3.
NMR struc: 20 models
Authors: M.Hilge,J.Aelen,A.Foarce,A.Perrakis,G.W.Vuister
Key ref: M.Hilge et al. (2009). Ca2+ regulation in the Na+/Ca2+ exchanger features a dual electrostatic switch mechanism. Proc Natl Acad Sci U S A, 106, 14333-14338. PubMed id: 19667209 DOI: 10.1073/pnas.0902171106
Date:
08-Jul-09     Release date:   18-Aug-09    
PROCHECK
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 Headers
 References

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     integral to membrane   1 term 
  Biological process     cell communication   1 term 

 

 
DOI no: 10.1073/pnas.0902171106 Proc Natl Acad Sci U S A 106:14333-14338 (2009)
PubMed id: 19667209  
 
 
Ca2+ regulation in the Na+/Ca2+ exchanger features a dual electrostatic switch mechanism.
M.Hilge, J.Aelen, A.Foarce, A.Perrakis, G.W.Vuister.
 
  ABSTRACT  
 
Regulation of ion-transport in the Na(+)/Ca(2+) exchanger (NCX) occurs via its cytoplasmic Ca(2+)-binding domains, CBD1 and CBD2. Here, we present a mechanism for NCX activation and inactivation based on data obtained using NMR, isothermal titration calorimetry (ITC) and small-angle X-ray scattering (SAXS). We initially determined the structure of the Ca(2+)-free form of CBD2-AD and the structure of CBD2-BD that represent the two major splice variant classes in NCX1. Although the apo-form of CBD2-AD displays partially disordered Ca(2+)-binding sites, those of CBD2-BD are entirely unstructured even in an excess of Ca(2+). Striking differences in the electrostatic potential between the Ca(2+)-bound and -free forms strongly suggest that Ca(2+)-binding sites in CBD1 and CBD2 form electrostatic switches analogous to C(2)-domains. SAXS analysis of a construct containing CBD1 and CBD2 reveals a conformational change mediated by Ca(2+)-binding to CBD1. We propose that the electrostatic switch in CBD1 and the associated conformational change are necessary for exchanger activation. The response of the CBD1 switch to intracellular Ca(2+) is influenced by the closely located cassette exons. We further propose that Ca(2+)-binding to CBD2 induces a second electrostatic switch, required to alleviate Na(+)-dependent inactivation of Na(+)/Ca(2+) exchange. In contrast to CBD1, the electrostatic switch in CBD2 is isoform- and splice variant-specific and allows for tailored exchange activities.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21157775 R.J.Falconer, and B.M.Collins (2011).
Survey of the year 2009: applications of isothermal titration calorimetry.
  J Mol Recognit, 24, 1.  
21209335 S.A.John, B.Ribalet, J.N.Weiss, K.D.Philipson, and M.Ottolia (2011).
Ca2+-dependent structural rearrangements within Na+-Ca2+ exchanger dimers.
  Proc Natl Acad Sci U S A, 108, 1699-1704.  
19815561 M.Wu, H.D.Le, M.Wang, V.Yurkov, A.Omelchenko, M.Hnatowich, J.Nix, L.V.Hryshko, and L.Zheng (2010).
Crystal structures of progressive Ca2+ binding states of the Ca2+ sensor Ca2+ binding domain 1 (CBD1) from the CALX Na+/Ca2+ exchanger reveal incremental conformational transitions.
  J Biol Chem, 285, 2554-2561.  
20187120 V.Breukels, and G.W.Vuister (2010).
Binding of calcium is sensed structurally and dynamically throughout the second calcium-binding domain of the sodium/calcium exchanger.
  Proteins, 78, 1813-1824.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time.