Differences in intradomain and interdomain motion confer distinct activation properties to structurally similar Gα proteins
| Autor: | Alan M. Jones, Janice C. Jones, Henrik G. Dohlman, Brenda Temple |
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| Rok vydání: | 2012 |
| Předmět: |
Models
Molecular Multidisciplinary Guanosine 5'-O-(3-Thiotriphosphate) Structural similarity Plasma protein binding GTP-Binding Protein alpha Subunits Gi-Go Molecular Dynamics Simulation Biological Sciences Biology Protein Structure Secondary Protein Structure Tertiary Molecular dynamics Biochemistry Helix Biophysics GTP-Binding Protein alpha Subunits Gq-G11 Amino Acid Sequence Receptor Peptide sequence Protein Binding |
| Zdroj: | Proceedings of the National Academy of Sciences. 109:7275-7279 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.1202943109 |
| Popis: | 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, Gα i1 and GPA1. Despite high structural similarity, GPA1 can activate itself without a receptor, whereas Gα i1 cannot. We found that motions in these proteins vary greatly in type and frequency. Whereas motion is greatest in the Ras domain of Gα i1 , 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 Gα i1 . Gα i1 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. |
| Databáze: | OpenAIRE |
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