Irina S Moreira1. 1. REQUIMTE/Departamento de Química e Bioquímica, Faculdade de Ciências da Universidade do Porto, Rua do Campo Alegre s/n, 4169-007 Porto, Portugal. Electronic address: irina.moreira@fc.up.pt.
Abstract
BACKGROUND: The details of the functional interaction between G proteins and the G protein coupled receptors (GPCRs) have long been subjected to extensive investigations with structural and functional assays and a large number of computational studies. SCOPE OF REVIEW: The nature and sites of interaction in the G-protein/GPCR complexes, and the specificities of these interactions selecting coupling partners among the large number of families of GPCRs and G protein forms, are still poorly defined. MAJOR CONCLUSIONS: Many of the contact sites between the two proteins in specific complexes have been identified, but the three dimensional molecular architecture of a receptor-Gα interface is only known for one pair. Consequently, many fundamental questions regarding this macromolecular assembly and its mechanism remain unanswered. GENERAL SIGNIFICANCE: In the context of current structural data we review the structural details of the interfaces and recognition sites in complexes of sub-family A GPCRs with cognate G-proteins, with special emphasis on the consequences of activation on GPCR structure, the prevalence of preassembled GPCR/G-protein complexes, the key structural determinants for selective coupling and the possible involvement of GPCR oligomerization in this process.
BACKGROUND: The details of the functional interaction between G proteins and the G protein coupled receptors (GPCRs) have long been subjected to extensive investigations with structural and functional assays and a large number of computational studies. SCOPE OF REVIEW: The nature and sites of interaction in the G-protein/GPCR complexes, and the specificities of these interactions selecting coupling partners among the large number of families of GPCRs and G protein forms, are still poorly defined. MAJOR CONCLUSIONS: Many of the contact sites between the two proteins in specific complexes have been identified, but the three dimensional molecular architecture of a receptor-Gα interface is only known for one pair. Consequently, many fundamental questions regarding this macromolecular assembly and its mechanism remain unanswered. GENERAL SIGNIFICANCE: In the context of current structural data we review the structural details of the interfaces and recognition sites in complexes of sub-family A GPCRs with cognate G-proteins, with special emphasis on the consequences of activation on GPCR structure, the prevalence of preassembled GPCR/G-protein complexes, the key structural determinants for selective coupling and the possible involvement of GPCR oligomerization in this process.
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