Structural Adaptation of Proteins to Different Biological Membranes

Abstract

Transmembrane polarity profiles and distributions of different protein groups that interact directly with lipids were calculated for 3D structuresof 187 α-helical and 73 β-barrel proteins from eight types of biological membranes. The polarity profiles were represented by H-bonding donor and acceptor capacities (α and β) and polarizability parameter (π∗) calculated for protein surface. The proteins from the set have different hydrophobic thicknesses, with average values of 23.1, 27.3 and 32.5 Å for outer bacterial, inner mitochondrial and eukaryotic plasma membranes, respectively, and 29.5 to 30.6Å for endoplasmic reticulum, thylakoid and different bacterial membranes. The proteins have three distinct polarity regions: lipid head group area with peaks for positively charged groups and crystallized water (15 to 25Å from the bilayer center); interfacial “mid-polar” region with peaks for Tyr and Trp (8 to 15Å); and aliphatic hydrocarbon core (±8Å). Polarity of the core region was nearly identical for different membranes (α∼0.01, β∼0.04, π∗=0.09-0.14). Main changes in polarity occur at the level of lipid carbonyl groups (∼15±5Å), but the changes are more gradual than in DOPC bilayer. The locations and amplitudes of peaks for Trp, Tyr, and Phe are frequently asymmetric and dependent on the type of membrane. The distributions of crystallized water have two peaks at ±20Å. Head groups of crystallized lipids are shitted closer to the hydrocarbon boundary, especially in mitochondrial membrane and on the inner side of eukaryotic plasma membrane. All proteins have a peak of positive net charge at ∼20 Å on the inner side, consistent with the “positive inside” rule, except single-chain β-barrels that follow “negative inside” rule. All curves are shifted inwards in β-barrels, consistent with their smaller thickness. Computational modeling of membrane proteins can be improved using hydrophobic thicknesses and asymmetric polarity profiles for different membranes.