Structural determinants of the supramolecular organization of G protein-coupled receptors in bilayers.

摘要: The G protein-coupled receptor (GPCR) rhodopsin self-assembles into supramolecular structures in native bilayers, but the structural determinants of oligomerization are not known. We carried out multiple self-assembly coarse-grained molecular dynamics (CGMD) simulations model membranes containing up to 64 molecules visual over time scales reaching 100 μs. show strong preferential interaction modes between receptors. Two primary receptor–receptor interactions consistent with umbrella sampling/potential mean force (PMF) calculations as a function distance pair interfaces, involving helices (H) 1/8, 4/5 and 5, present no energy barrier forming very stable dimer. Most notably, PMFs that preferred dimer exists tail-to-tail conformation, interface comprising transmembrane H1/H2 amphipathic H8 at extracellular cytoplasmic surfaces, re...