A coarse-grained simulation survey of lipid-protein interactions of several P-type ATPases

MAURICIO SICA; FLORENCIA PIGNATARO; JOSE MARIA DELFINO; JUAN PABLO ROSSI; IRENE MANGIALAVORI

Congreso; XLVII Reunión Annual de la Sociedad de Biofísica Argentina.; 2018

Free fatty acids are known to regulate the function of several membrane proteins modulating the structure of membranes or interacting with the proteins. Specifically, there are growing evidence that oleic (OA) and linoleic (LA) acids present in membranes are natural compounds that regulate the function of Na+,K+-ATPase (1) and plasma membrane calcium ATPase (PMCA) (2). In this work we used coarse-grained simulations to compare lipid-protein interactions of several P-type ATPases. Using the Martini coarse-grained forcefield we simulated PMCA, sarcoplasmic calcium ATPase (SERCA) and Na+,K+-ATPase embeded in membranes composed of DLPC, DOPC and OA. The protein coarse-grained models were prepared from PBD structures of SERCA and Na+,K+-ATPase (codes 1t8s and 2zxe, respectively). The input all-atom structure of PMCA was obtained by homology with SERCA using an alignment reported by Penniston (3) and the Modeller software (the autoinhibitory domain was excluded). At least 5 independent simulations of 5 microseconds were performed for each protein. Analyses suggest that although the transmembrane architecture is shared, the lipid-protein interactions comprise a unique fingerprint which involves a range of asymmetric distributions, non-specific and specific interactions. Particularly, our simulations highlight specific interactions of OA with Na+,K+-ATPase and PMCA, absent in SERCA.