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Theoretical study of the electrostatically driven step of receptor‐G protein recognition
Author(s) -
Fanelli Francesca,
Menziani Cristina,
Scheer Alexander,
Cotecchia Susanna,
De Benedetti Pier G.
Publication year - 1999
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/(sici)1097-0134(19991101)37:2<145::aid-prot1>3.0.co;2-r
Subject(s) - receptor , neuroscience , chemistry , computer science , biophysics , psychology , biology , biochemistry
This study proposes a theoretical model describing the electrostatically driven step of the α1b‐adrenergic receptor (AR)‐G protein recognition. The comparative analysis of the structural‐dynamics features of functionally different receptor forms, i.e., the wild type (ground state) and its constitutively active mutants D142A and A293E, was instrumental to gain insight on the receptor‐G protein electrostatic and steric complementarity. Rigid body docking simulations between the different forms of the α1b‐AR and the heterotrimeric Gαq, Gαs, Gαi1, and Gαt suggest that the cytosolic crevice shared by the active receptor and including the second and the third intracellular loops as well as the cytosolic extension of helices 5 and 6, represents the receptor surface with docking complementarity with the G protein. On the other hand, the G protein solvent‐exposed portions that recognize the intracellular loops of the activated receptors are the N‐terminal portion of α3, αG, the αG/α4 loop, α4, the α4/β6 loop, α5, and the C‐terminus. Docking simulations suggest that the two constitutively active mutants D142A and A293E recognize different G proteins with similar selectivity orders, i.e., Gαq ≈ =Gαs > Gαi > > Gαt. The theoretical models herein proposed might provide useful suggestions for new experiments aiming at exploring the receptor‐G protein interface. Proteins 1999;37:145–156. ©1999 Wiley‐Liss, Inc.