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

DELFINO, JOSÉ M; MARÍA FLORENCIA PIGNATARO; IRENE C. MANGIALAVORI; SICA, MAURICIO P; JUAN PABLO F. C. ROSSI

La Plata

Congreso; XLVII Reunión Anual SAB; 2018

Sociedad Argentina de Biofísica

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 in membranes composed of DLPC, DOPC and OA. Protein models were prepared from PBD structures of SERCA and Na+,K+-ATPase (1t8s and 2zxe, respectively). The all-atom structure of PMCA was built by homology with SERCA using an curated alignment (3) with Modeller (autoinhibitory domain was excluded). Five independent 5-usecs simulations were performed for each protein. 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.