The fourth transmembrane segment forms the interface of the dopamine D2 receptor homodimer
Guo, W.; Shi, L.; Javitch, J.A.
Journal of Biological Chemistry 278(7): 4385-4388
ISSN/ISBN: 0021-9258 PMID: 12496294 DOI: 10.1074/jbc.c200679200
Considerable evidence suggests that G-protein-coupled receptors form homomeric and heteromeric dimers in vivo. Unraveling the structural mechanism for cross-talk between receptors in a dimeric complex must start with the identification of the presently unknown dimer interface. Here, by using cysteine cross-linking, we identify the fourth transmembrane segment (TM4) as a symmetrical dimer interface in the dopamine D2 receptor. Cross-linking is unaffected by ligand binding, and ligand binding and receptor activation are unaffected by cross-linking, suggesting that the receptor is a constitutive dimer. The accessibility of adjacent residues in TM4, however, is affected by ligand binding, implying that the interface has functional significance.