Deciphering the Mechanism of Inhibition of SERCA1a by Sarcolipin Using Molecular Simulations.

ABSTRACT: SERCA1a is an ATPase calcium pump that transports Ca²⁺ from the cytoplasm to the sarco/endoplasmic reticulum lumen. Sarcolipin (SLN), a transmembrane peptide, regulates the activity of SERCA1a by decreasing its Ca²⁺ transport rate, but its mechanism of action is still not well-understood. To decipher this mechanism, we have performed normal mode analysis in the all-atom model, with the SERCA1a-SLN complex, or the isolated SERCA1a, embedded in an explicit membrane. The comparison of the results allowed us to provide an explanation at the atomic level for the action of SLN that is in good agreement with experimental observations. In our analyses, the presence of SLN locally perturbs the TM6 transmembrane helix and as a consequence modifies the position of D800, one of t

SUBMITTER: Barbot T 

PROVIDER: S-EPMC7890198 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature