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Probing Gai1 protein activation at single-amino acid resolution
- Source :
- Nature Structural & Molecular Biology, Nat Struct Mol Biol, Europe PubMed Central
- Publication Year :
- 2015
-
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.
- Subjects :
- Alanine
chemistry.chemical_classification
Models, Molecular
Rhodopsin
Chemistry
Stereochemistry
Protein Conformation
Protein Stability
Protein subunit
DNA Mutational Analysis
Plasma protein binding
GTPase
DNA
Article
GTP-Binding Protein alpha Subunits
Protein structure
Structural Biology
Helix
Cluster (physics)
Humans
Nucleotide
Amino Acids
Molecular Biology
Protein Binding
Subjects
Details
- Volume :
- 22
- Issue :
- 9
- Database :
- OpenAIRE
- Journal :
- Nature Structural & Molecular Biology
- Accession number :
- edsair.doi.dedup.....47b3110c32bbc414fa8b9480f703bf3e
- Full Text :
- https://doi.org/10.1038/nsmb.3070