Long-range dynamic effects of point mutations propagate through side chains in the serine protease inhibitor eglin c.


Abstract

Long-range interactions are fundamental to protein behaviors such as cooperativity and allostery. In an attempt to understand the role protein flexibility plays in such interactions, the distribution of local fluctuations in a globular protein was monitored in response to localized, nonelectrostatic perturbations. Two valine-to-alanine mutations were introduced into the small serine protease inhibitor eglin c, and the (15)N and (2)H NMR spin relaxation properties of these variants were analyzed in terms of the Lipari-Szabo dynamics formalism and compared to those of the wild type. Significant changes in picosecond to nanosecond dynamics were observed in side chains located as much as 13 A from the point of mutation. Additionally, those residues experiencing altered dynamics appear to form contiguous surfaces within the protein. In the case of V54A, the large-to-small mutation results in a rigidification of connected residues, even though this mutation decreases the global stability. These findings suggest that dynamic perturbations arising from single mutations may propagate away from the perturbed site through networks of interacting side chains. That this is observed in eglin c, a classically nonallosteric protein, suggests that such behavior will be observed in many, if not all, globular proteins. Differences in behavior between the two mutants suggest that dynamic responses will be context-dependent. Study holds ProTherm entries: 18378, 18379, 18380, 18381, 18382, 18383, 18384, 18385 Extra Details: long-range interactions; flexibility; nonelectrostatic perturbations; context-dependent

Submission Details

ID: AUUeRHVq

Submitter: Connie Wang

Submission Date: April 24, 2018, 8:50 p.m.

Version: 1

Publication Details
Clarkson MW;Lee AL,Biochemistry (2004) Long-range dynamic effects of point mutations propagate through side chains in the serine protease inhibitor eglin c. PMID:15449934
Additional Information

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