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• W2767479447 abstract "Abstract Tubulins are an ancient family of eukaryotic proteins characterized by an amino‐terminal globular domain and disordered carboxyl terminus. These carboxyl termini play important roles in modulating the behavior of microtubules in living cells. However, the atomic‐level basis of their function is not well understood. These regions contain multiple acidic residues and their overall charges are modulated in vivo by post‐translational modifications, for example, phosphorylation. In this study, we describe an application of NMR and computer Monte Carlo simulations to investigate how the modification of local charge alters the conformational sampling of the γ‐tubulin carboxyl terminus. We compared the dynamics of two 39‐residue polypeptides corresponding to the carboxyl‐terminus of yeast γ‐tubulin. One polypeptide comprised the wild‐type amino acid sequence while the second contained a Y > D mutation at Y11 in the polypeptide (Y445 in the full protein). This mutation introduces additional negative charge at a site that is phosphorylated in vivo and produces a phenotype with perturbed microtubule function. NMR relaxation measurements show that the Y11D mutation produces dramatic changes in the millisecond‐timescale motions of the entire polypeptide. This observation is supported by Monte Carlo simulations that—similar to NMR—predict the WT γ‐CT is largely unstructured and that the substitution of Tyr 11 with Asp causes the sampling of extended conformations that are unique to the Y11D polypeptide." @default.
• W2767479447 created "2017-11-17" @default.
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• W2767479447 date "2017-12-15" @default.
• W2767479447 modified "2023-09-29" @default.
• W2767479447 title "Concerted millisecond timescale dynamics in the intrinsically disordered carboxyl terminus of γ-tubulin induced by mutation of a conserved tyrosine residue" @default.
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• W2767479447 doi "https://doi.org/10.1002/pro.3345" @default.
• W2767479447 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5775176" @default.
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• W2767479447 hasPublicationYear "2017" @default.
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