We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Frustration Sculpts the Early Stages of Protein Folding.
- Authors
Di Silvio, Eva; Brunori, Maurizio; Gianni, Stefano
- Abstract
The funneled energy landscape theory implies that protein structures are minimally frustrated. Yet, because of the divergent demands between folding and function, regions of frustrated patterns are present at the active site of proteins. To understand the effects of such local frustration in dictating the energy landscape of proteins, here we compare the folding mechanisms of the two alternative spliced forms of a PDZ domain (PDZ2 and PDZ2as) that share a nearly identical sequence and structure, while displaying different frustration patterns. The analysis, based on the kinetic characterization of a large number of site-directed mutants, reveals that although the late stages for folding are very robust and biased by native topology, the early stages are more malleable and dominated by local frustration. The results are briefly discussed in the context of the energy-landscape theory.
- Subjects
PROTEIN folding; PROTEIN conformation; PROTEIN splicing; CHEMICAL reactions; CHEMICAL research
- Publication
Angewandte Chemie, 2015, Vol 127, Issue 37, p11017
- ISSN
0044-8249
- Publication type
Article
- DOI
10.1002/ange.201504835