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Theoretical study on receptor–G protein recognition: New insights into the mechanism of the α1b‐adrenergic receptor activation
Author(s) -
Fanelli Francesca,
Menziani Cristina,
Scheer Alexander,
Cotecchia Susanna,
De Benedetti Pier G.
Publication year - 1999
Publication title -
international journal of quantum chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.484
H-Index - 105
eISSN - 1097-461X
pISSN - 0020-7608
DOI - 10.1002/(sici)1097-461x(1999)73:2<71::aid-qua3>3.0.co;2-3
Subject(s) - cytosol , agonist , receptor , chemistry , in silico , biophysics , docking (animal) , mutant , helix (gastropod) , intracellular , stereochemistry , biochemistry , enzyme , biology , gene , medicine , ecology , nursing , snail
This work compares the structural/dynamics features of the wild‐type α1b‐adrenergic receptor (AR) with those of the D142A active mutant and the agonist‐bound state. The two active receptor forms were compared in their isolated states as well as in their ability to form homodimers and to recognize the Gαqβ1γ2 heterotrimer. The analysis of the isolated structures revealed that, although the mutation‐ and agonist‐induced active states of the α1b‐AR are different, they, however, share several structural peculiarities including (a) the release of some constraining interactions found in the wild‐type receptor and (b) the opening of a cytosolic crevice formed by the second and third intracellular loops and the cytosolic extensions of helices 5 and 6. Accordingly, also their tendency to form homodimers shows commonalties and differences. In fact, in both the active receptor forms, helix 6 plays a crucial role in mediating homodimerization. However, the homodimeric models result from different interhelical assemblies. On the same line of evidence, in both of the active receptor forms, the cytosolic opened crevice recognizes similar domains on the G protein. However, the docking solutions are differently populated and the receptor–G protein preorientation models suggest that the final complexes should be characterized by different interaction patterns. ©1999 John Wiley & Sons, Inc. Int J Quant Chem 73: 71–83, 1999