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[摘要]：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 G alpha proteins, G alpha(i1) and GPA1. Despite high structural similarity, GPA1 can activate itself without a receptor, whereas G alpha(i1) cannot. We found that motions in these proteins vary greatly in type and frequency. Whereas motion is greatest in the Ras domain of G alpha(i1), it is greatest in helices alpha A and alpha B from the helical domain of GPA1. Using protein chimeras, we show that helix alpha A from GPA1 is sufficient to confer rapid activation to G alpha(i1). G alpha(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. |
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