Journal of Proteomics & Bioinformatics
Open Access
ISSN: 0974-276X
+44 1223 790975
ISSN: 0974-276X
+44 1223 790975
Liliane Mouawad
Institut Curie, France
Scientific Tracks Abstracts: J Proteomics Bioinform
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. Throughout 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. This conformational transition is enhanced by ATP phosphorylation which occurs after Ca2+ binding by SERCA1a. Sarcolipin (SLN), a transmembrane helix of 31 residues regulates SERCA1a by diminishing its affinity to Ca2+. The mechanism of this regulation is not elucidated yet despite the knowledge of the crystal structure (see figure). 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. This 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 difficult in the presence of SLN, because of some specific interactions with SERCA1a that result in additional fluctuations of SERCA1a-SLN. A long-distance transmission of information (over 35 �?) within the protein was also observed, explaining the phosphorylation difficulty in the complex. These results provide new insights into the mechanism of the SERCA1a enzymatic cycle and its regulation by SLN. Recent Publications 1. Chaput L and Mouawad L (2017) Efficient conformational sampling and weak scoring in docking programs? Strategy of the wisdom of crowds. Journal of Cheminformatics 9:37. 2. Domingues M J, Martinez�??Sanz J, Papon L, Larue L, Mouawad L and Bonaventure J (2017) Structure-based mutational analysis of ICAT residues mediating negative regulation of β-catenin co-transcriptional activity. Plos One DOI:10.1371/ journal.pone.0172603. 3. Chaput L, Martinez�??Sanz J, Saettel N and Mouawad L (2016) Benchmark of four popular virtual screening programs: construction of the active/decoy dataset remains a major determinant of measured performance. Journal of Cheminformatics 8:56. 4. Chaput L, Martinez�??Sanz J, Quiniou E, Rigolet P, Saettel N and Mouawad L (2016) vSDC: a method to improve early recognition in virtual screening when limited experimental resources are available. Journal of Cheminformatics 8:1. 5. Quiniou E, Guichard P, Perahia D, Marco S and Mouawad L (2013) An atomistic view of microtubule stabilization by GTP. Structure 21:833�??843.