Theoretical study on receptor–G protein recognition: New insights into the mechanism of the α1b-adrenergic receptor activation
✍ Scribed by Francesca Fanelli; Cristina Menziani; Alexander Scheer; Susanna Cotecchia; Pier G. De Benedetti
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- English
- Weight
- 716 KB
- Volume
- 73
- Category
- Article
- ISSN
- 0020-7608
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✦ Synopsis
This work compares the structuralrdynamics features of the wild-type Ž . ␣1b-adrenergic receptor AR with those of the D142A active mutant and the agonistbound 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 G␣q  1␥ 2 heterotrimer. The analysis of the isolated structures revealed that, although the mutation-and agonistinduced active states of the ␣1b-AR are different, they, however, share several structural Ž . peculiarities including a the release of some constraining interactions found in the Ž . 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.