Lipid Composition Modulates Membrane Protein Clustering

Abstract

It is well-established that membranes are complex, crowded environments but better understanding is needed of the in vivo molecular-level organization. High resolution structures are static or capture only isolated parts of the whole system. Super resolution optical imaging methods can be used to observe dynamic processes in intact cell membranes but often at the expense of atomic resolution. Molecular dynamics have been used recently to study the nanoscale organization of the plasma membrane [1,2] and the formation of outer membrane protein clusters in the E. coli outer membrane [3].Inward rectifier potassium (Kir) channels are a family of channels that are activated by interaction with PIP2 at specific sites [4]. Their activity is also regulated by specific protein-lipid interactions with other anionic lipids in the membrane [5], and cholesterol [6].In order to explore the organisation of Kir channels in cell membranes we have use coarse-grained molecular dynamics simulations of a patch of membrane containing over 100 Kir2.2 channels, with lipid composition ranging from plasma membrane-like to a one-lipid component membrane.We show that lipid composition modulates Kir channel diffusion and clustering: diffusion rates decrease with increased lipid complexity, which in turn modulates the size and shape of protein clusters.1. Koldso et al (2014) PLoS Comp. Biol. 10:e10039112. Ingolfsson et al (2014) J Am Chem Soc 136(41):14554-93. Rassam et al (2015) Nature 16;523(7560):333-64. Hansen et al (2011) Nature 477(7365):495-85. Lee et al (2013) Nat Commun 4:27866. D'Avanzo et al (2011) PLoS One 6(4):e19393