Published in

National Academy of Sciences, Proceedings of the National Academy of Sciences, 35(115), 2018

DOI: 10.1073/pnas.1807379115

Links

Tools

Export citation

Search in Google Scholar

The consequences of cavity creation on the folding landscape of a repeat protein depend upon context

This paper was not found in any repository, but could be made available legally by the author.
This paper was not found in any repository, but could be made available legally by the author.

Full text: Unavailable

Red circle
Preprint: archiving forbidden
Green circle
Postprint: archiving allowed
Red circle
Published version: archiving forbidden
Data provided by SHERPA/RoMEO

Abstract

Significance Extant protein sequences are the result of evolutionary pressure. Eliminating core packing interactions by mutation, regardless of position, generally results in similar perturbations to global stability. In contrast, we find that cavity creation has highly varied consequences for a protein folding landscape, depending upon the context in which the cavities are introduced. These observations have implications for interpreting evolutionary adaptation, as it is likely that proteins have evolved to exhibit optimal levels of conformational heterogeneity and dynamics. These results should also inform protein engineering efforts, as they provide insight into how sequence can modulate the population of functionally important excited states, as well as states that lead to secondary, undesirable reactions such as oligomerization, aggregation, surface activity, and phase separation.