title: Calcium binding and allosteric signaling mechanisms for the sarcoplasmic reticulum Ca²+ ATPase.
abstract: 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.
authors: Department of Pharmacology, University of California, San Diego, La Jolla, California 92093, USA. pkekeneshuskey@ucsd.edu
authors: Peter M
authors: PM
authors: Kekenes-Huskey
authors: Vincent T
authors: VT
authors: Metzger
authors: Barry J
authors: BJ
authors: Grant
authors: J
authors: J
authors: Andrew McCammon
mesh_terms: D001665:Binding Sites; D002118:Calcium / Q000737:chemistry / Q000378:metabolism*; D020013:Calcium Signaling; D030562:Databases, Protein; D056004:Molecular Dynamics Simulation; D025341:Principal Component Analysis; D017434:Protein Structure, Tertiary; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000737:chemistry / Q000378:metabolism*; D013816:Thermodynamics
chemical_list: D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D002118:Calcium