Frustration Sculpts the Early Stages of Protein Folding1. Issue 37 (23rd July 2015)

• Record Type: Journal Article
• Authors: Di Silvio, Eva; Brunori, Maurizio; Gianni, Stefano
• Is Part Of: Angewandte Chemie international edition. Volume 54:Issue 37(2015)
• Page Start: 10867
• Page End: 10869
• Publication Date: 2015-07-23
• Subjects: Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201504835
• Languages: English
• ISSNs: 1433-7851

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>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.</p> </abstract>