Molecular modeling of transmembrane helices 6 and 7 of the heptahelical lutropin receptor.
In response to ligand binding and activating mutations, the lutropin receptor undergoes a conformational change to trigger a cellular response. D556 is the most common locus for naturally occurring activating mutations of the lutropin receptor, and a D556A mutant is shown to be constitutively active. A water-mediated proton transfer is postulated as part of the transmembrane signaling mechanism. Using energy minimization and ab initio calculations, a hydrogen bonding network involving a highly constrained water molecule(s) and D556 (helix 6) and N593/N597/Y601 (helix 7) is presented.
Department of Biochemistry & Molecular Biology, University of Georgia, Athens 30602, USA.
J Paul
JP
Simon
Krassimira
K
Angelova
David
D
Puett
D000818:Animals; D019556:COS Cells; D002462:Cell Membrane / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D006860:Hydrogen Bonding; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D011522:Protons; D051381:Rats; D011974:Receptors, LH / Q000737:chemistry* / Q000235:genetics*; D015398:Signal Transduction; D014867:Water / Q000737:chemistry
D018076:DNA, Complementary; D011522:Protons; D011974:Receptors, LH; D014867:Water; D000242:Cyclic AMP