Lipid-Mediated Interactions between Intrinsic Membrane Proteins: Dependence on Protein Size and Lipid Composition

Abstract

The present study is an application of an approach recently developed by the authors for describing the structure of the hydrocarbon chains of lipid-bilayer membranes (LBMs) around embedded protein inclusions ( Biophys. J. 79:2867-2879). The approach is based on statistical mechanical integral equation theories developed for the study of dense liquids. First, the configurations extracted from molecular dynamics simulations of pure LBMs are used to extract the lateral density-density response function. Different pure LBMs composed of different lipid molecules were considered: dioleoyl phosphatidylcholine (DOPC), palmitoyl-oleoyl phosphatidylcholine (POPC), dipalmitoyl phosphatidylcholine (DPPC), and dimyristoyl phosphatidylcholine (DMPC). The results for the lateral density-density response function was then used as input in the integral equation theory. Numerical calculations were performed for protein inclusions of three different sizes. For the sake of simplicity, protein inclusions are represented as hard smooth cylinders excluding the lipid hydrocarbon core from a small cylinder of 2.5 A radius, corresponding roughly to one aliphatic chain, a medium cylinder of 5 A radius, corresponding to one alpha-helix, and a larger cylinder of 9 A radius, representing a small protein such as the gramicidin channel. The lipid-mediated interaction between protein inclusions was calculated using a closed-form expression for the configuration-dependent free energy. This interaction was found to be repulsive at intermediate range and attractive at short range for two small cylinders in POPC, DPPC, and DMPC bilayers, whereas it oscillates between attractive and repulsive values in DOPC bilayers. For medium size cylinders, it is again repulsive at intermediate range and attractive at short range, but for every model LBM considered here. In the case of a large cylinder, the lipid-mediated interaction was shown to be repulsive for both short and long ranges for the DOPC, POPC, and DPPC bilayers, whereas it is again repulsive and attractive for DMPC bilayers. The results indicate that the packing of the hydrocarbon chains around protein inclusions in LBMs gives rise to a generic (i.e., nonspecific) lipid-mediated interaction which favors the association of two alpha-helices and depends on the lipid composition of the membrane.

Interaction between two cylindrical inclusions in a symmetric lipid bilayer

“…[23][24][25][26][27][28] These models generally take the conformational freedom of individual lipid chains into account. For example, Fattal and Ben-Shaul 29 have used a chain packing theory to calculate the free energy of the interaction between a large inclusion ͑represented as a long wall of length L) and a lipid bilayer, as a function of the hydrophobic mismatch.…”

“…In between, for protein-protein distances somewhat larger than the lipid diameter, a repulsive energy barrier occurred. In another series of studies Lagüe et al 27,28 have applied hypernetted chain integral equation formalism to a lipid bilayerlike fluid medium. The lateral density-density response function of the hydrophobic core was extracted from MD simulations.…”

Rigidity of transmembrane proteins determines their cluster shape

“…In contrast to previous studies [4,[15][16][17] where hydrophobic mismatch is considered to be essential for clustering, we showed that proteins form stable clusters even in the absence of mismatch. Lipidinduced depletion interactions have been suggested as one of the main contributing factors to the interactions of cylindrical inclusions in bilayers [4,29,30]. This type of attraction occurs at distances smaller than the diameter of one lipid molecule.…”

“…However, the shape of the clusters is determined by a repulsive zone when proteins are close to each other and form groups of three or more proteins. The repulsive zone occurs when the distances between proteins are slightly larger than the size of one lipid molecule (beyond the depletion zone) [29,30]. When a dimer forms, the fluctuation-induced attraction between proteins overcomes the effect of the repulsive zone and RPs and SFPs are able to create string-like aggregates at the early stages of simulations.…”

Efeitos de pesticidas sobre a fragilidade osmótica de eritrócitos – Uma breve revisão

“…As proteínas estão mergulhadas na bicamada (proteínas intrínsecas) ou estão na superfície interna ou externa da bicamada lipídica (proteínas extrínsecas) (Lague et al, 2001). As membranas de organelas subcelulares tais como mitocôndrias e núcleos raramente contêm colesterol (Halliwel e Gutteridge, 1999).…”