G protein-coupled receptors (GPCRs) form the largest family of membrane proteins in the human genome and are involved in important physiological functions. Therefore, they are very attractive pharmacological targets for the pharmaceutical industry. Although GPCRs have traditionally been described as monomeric receptors, they also ...»»»»
G protein-coupled receptors (GPCRs) form the largest family of membrane proteins in the human genome and are involved in important physiological functions. Therefore, they are very attractive pharmacological targets for the pharmaceutical industry. Although GPCRs have traditionally been described as monomeric receptors, they also form homodimers, heterodimers, and higher-order oligomers, with specific functions different from those of individual receptors. The growth of the number of crystal structures in recent years provided many crystallographic protomer-protomer contacts that may be feasible in the cell membrane (including homodimers, homotrimers and homotetramers). Although these structures do not necessary represent biologically relevant states, they could be used as a starting point to understand the interactions that determine the formation of dimer. In the present work we aim to quantitatively evaluate these contacts by using molecular dynamics of 58 different crystallographic dimers. We conclude that 34 interfaces may represent actual dimers, 25 in the head-to-head model and 9 the head-to-tail mode. The results may help to develop structural models of homomers and heteromers of GPCR.^^^^
