Key result
Molecular and Brownian dynamics simulations revealed that surface-exposed polar residues and Glu309 gating play crucial roles in the diffusional encounter and binding of Ca2+ to SERCA.
Key points are not available for this paper at this time.
Hypothesis-generating for SERCA Ca2+ dynamics; leaves open whether residue targeting alters cardiac calcium handling in vivo.
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.
No takes yet. Share an insight, caveat, or question.
Kekenes–Huskey et al. (2012) studied this question. Molecular and Brownian dynamics simulations revealed that surface-exposed polar residues and Glu309 gating play crucial roles in the diffusional encounter and binding of Ca2+ to SERCA.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: