AI Article Synopsis
- We created detailed maps showing the specific amino acids that help stabilize the Gαi1 protein in both nucleotide- and receptor-bound forms.
- By observing how mutations in these amino acids affected stability, we found important areas (stabilization clusters) in the GTPase and helical domains that are crucial for maintaining structure and enabling activation.
- Key residues, like Y320 and F336, play significant roles in stabilizing the protein in its various states, and changes in helix α1 can disrupt crucial interactions, leading to the release of GDP.
Article Abstract
We present comprehensive maps at single-amino acid resolution of the residues stabilizing the human Gαi1 subunit in nucleotide- and receptor-bound states. We generated these maps by measuring the effects of alanine mutations on the stability of Gαi1 and the rhodopsin-Gαi1 complex. We identified stabilization clusters in the GTPase and helical domains responsible for structural integrity and the conformational changes associated with activation. In activation cluster I, helices α1 and α5 pack against strands β1-β3 to stabilize the nucleotide-bound states. In the receptor-bound state, these interactions are replaced by interactions between α5 and strands β4-β6. Key residues in this cluster are Y320, which is crucial for the stabilization of the receptor-bound state, and F336, which stabilizes nucleotide-bound states. Destabilization of helix α1, caused by rearrangement of this activation cluster, leads to the weakening of the interdomain interface and release of GDP.
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Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4876908 | PMC |
| http://dx.doi.org/10.1038/nsmb.3070 | DOI Listing |
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