Calcium binding and allosteric signaling mechanisms for the sarcoplasmic reticulum Ca²+ ATPase

Protein Sci. 2012 Oct;21(10):1429-43. doi: 10.1002/pro.2129.


The sarcoplasmic reticulum Ca²⁺ 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 Ca²⁺-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 Ca²⁺. Molecular dynamics simulations indicate the role of Glu309 gating in binding Ca²⁺, 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 Ca²⁺ binding and catalytic transitions.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Binding Sites
  • Calcium / chemistry
  • Calcium / metabolism*
  • Calcium Signaling*
  • Databases, Protein
  • Molecular Dynamics Simulation
  • Principal Component Analysis
  • Protein Structure, Tertiary
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases / chemistry
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases / metabolism*
  • Thermodynamics


  • Sarcoplasmic Reticulum Calcium-Transporting ATPases
  • Calcium