Proceedings of the National Academy of Sciences - PNAS, 2012-05, Vol.109 (19), p.7275-7279
2012
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- Autor(en) / Beteiligte
- Titel
- Differences in intradomain and interdomain motion confer distinct activation properties to structurally similar Gα proteins
- Ist Teil von
- Proceedings of the National Academy of Sciences - PNAS, 2012-05, Vol.109 (19), p.7275-7279
- Ort / Verlag
- United States: National Academy of Sciences
- Erscheinungsjahr
- 2012
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Proteins with similar crystal structures can have dissimilar rates of substrate binding and catalysis. Here we used molecular dynamics simulations and biochemical analysis to determine the role of intradomain and interdomain motions in conferring distinct activation rates to two Gα proteins, Gαi1 and GPA1. Despite high structural similarity, GPA1 can activate itself without a receptor, whereas Gαi1 cannot. We found that motions in these proteins vary greatly in type and frequency. Whereas motion is greatest in the Ras domain of Gαi1, it is greatest in helices αA and αB from the helical domain of GPA1. Using protein chimeras, we show that helix αA from GPA1 is sufficient to confer rapid activation to Gαi1. Gαi1 has less intradomain motion than GPA1 and instead displays interdomain displacement resembling that observed in a receptor–heterotrimer crystal complex. Thus, structurally similar proteins can have distinct atomic motions that confer distinct activation mechanisms.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0027-8424eISSN: 1091-6490DOI: 10.1073/pnas.1202943109Titel-ID: cdi_jstor_primary_41593005
- Format
- –
- Schlagworte
- Amino Acid Sequence, Biological Sciences, catalytic activity, Chimeras, chimerism, Crystal structure, Exchange rates, GTP-Binding Protein alpha Subunits, Gi-Go - chemistry, GTP-Binding Protein alpha Subunits, Gi-Go - metabolism, GTP-Binding Protein alpha Subunits, Gq-G11 - chemistry, GTP-Binding Protein alpha Subunits, Gq-G11 - metabolism, Guanine nucleotides, Guanosine 5'-O-(3-Thiotriphosphate) - chemistry, Guanosine 5'-O-(3-Thiotriphosphate) - metabolism, Hydrolysis, Kinetics, Models, Molecular, Molecular dynamics, Molecular Dynamics Simulation, Nucleotides, Protein Binding, Protein Structure, Secondary, Protein Structure, Tertiary, Proteins, Receptors