Update 1 of: Computational Modeling Approaches to Structure-Function Analysis of G Protein-Coupled Receptors

Computational modeling approaches to structure function analysis of G protein-coupled receptors are discussed. Using mouse luteinizing hormone receptor (LHR) as a model GPCR, it was demonstrated that transgenic mice coexpressing binding-deficient and signaling-deficient forms of LHR can reestablish normal LH actions through intermolecular functional complementation of the mutant receptors in the absence of functional wild type receptors. study on a stabilized and purified heterodimer of BLT1 indicated that although ligand binding to one protomer in the heterodimer is associated with cross-conformational changes, a transactivation mechanism where the ligand-free subunit would trigger GDP/GTP exchange is unfeasible. It is also found that the representation of GPCR structures as networks of interacting amino acids can be a way to decipher the impact of ligand and dimerization/oligomerization on the molecular communication intrinsic to the protein fold, which is likely to serve to protein stability and function. It may represent also a tool to highlight asymmetry in supramolecular assemblies.