Structural Biology

The Ca2+ pump SERCA1a is a P-type ATPase, localized in the sarcoplasmic reticulum membrane of striated muscle cells.

SERCA1a is involved in the contraction/relaxation process by fast pumping the cytoplasmic Ca2+ into the reticulum.

Th roughout its catalytic cycle, SERCA1a presents two major conformations: the E1 conformation where its Ca2+ channel is open

toward the cytoplasm and the E2 conformation where this channel is open toward the lumen. Th is conformational transition

is enhanced by ATP phosphorylation which occurs aft er Ca2+ binding by SERCA1a. Sarcolipin (SLN), a transmembrane helix

of 31 residues regulates SERCA1a by diminishing its affi nity to Ca2+. Th e mechanism of this regulation is not elucidated yet

despite the knowledge of the crystal structure (see fi gure). To decipher this mechanism, we performed normal mode analysis

(NMA), in the all-atom model on two systems, in the presence and the absence of SLN in a POPC membrane and one layer of

water for the soluble parts of the protein. Th is analysis showed that both systems are prone to go toward the conformation of

2Ca2+ E1 more easily than toward that of E2. However, both transitions seem more diffi cult in the presence of SLN, because of

some specifi c interactions with SERCA1a that result in additional fl uctuations of SERCA1a-SLN. A long-distance transmission

of information (over 35 Å) within the protein was also observed, explaining the phosphorylation diffi culty in the complex.

Th ese results provide new insights into the mechanism of the SERCA1a enzymatic cycle and its regulation by SLN.