The fourth transmembrane segment forms the interface of the dopamine D2 receptor homodimer.
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.
Guo
Wen
W
Center for Molecular Recognition, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.
Shi
Lei
L
Javitch
Jonathan A
JA
D001665:Binding Sites / Q000235:genetics; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D003432:Cross-Linking Reagents; D003545:Cysteine; D006801:Humans; D008024:Ligands; D009154:Mutation; D017448:Receptors, Dopamine D2 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
D003432:Cross-Linking Reagents; D008024:Ligands; D017448:Receptors, Dopamine D2; D003545:Cysteine