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Calcium binding and allosteric signaling mechanisms for the sarcoplasmic reticulum Ca 2+ ATPase
Author(s) -
KekenesHuskey Peter M.,
Metzger Vincent T.,
Grant Barry J.,
Andrew McCammon J.
Publication year - 2012
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1002/pro.2129
Subject(s) - serca , endoplasmic reticulum , chemistry , biophysics , plasma membrane ca2+ atpase , calcium atpase , allosteric regulation , calcium , calcium pump , cytosol , atpase , calmodulin , gating , biochemistry , enzyme , biology , organic chemistry
The sarcoplasmic reticulum Ca 2+ ATPase (SERCA) is a membrane‐bound pump that utilizes ATP to drive calcium ions from the myocyte cytosol against the higher calcium concentration in the sarcoplasmic reticulum. Conformational transitions associated with Ca 2+ ‐binding are important to its catalytic function. We have identified collective motions that partition SERCA crystallographic structures into multiple catalytically‐distinct states using principal component analysis. Using Brownian dynamics simulations, we demonstrate the important contribution of surface‐exposed, polar residues in the diffusional encounter of Ca 2+ . Molecular dynamics simulations indicate the role of Glu309 gating in binding Ca 2+ , as well as subsequent changes in the dynamics of SERCA's cytosolic domains. Together these data provide structural and dynamical insights into a multistep process involving Ca 2+ binding and catalytic transitions.

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