Rerouting the folding pathway of the Notch ankyrin domain by reshaping the energy landscape.

ABSTRACT: The modular nature of repeat proteins has made them a successful target for protein design. Ankyrin repeat, TPR, and leucine rich repeat domains that have been designed solely on consensus information have been shown to have higher thermostability than their biological counterparts. We have previously shown that we can reshape the energy landscape of a repeat protein by adding multiple C-terminal consensus ankyrin repeats to the five N-terminal repeats of the Notch ankyrin domain. Here we explore how the folding mechanism responds to reshaping of the energy landscape. We have used analogous substitutions of a conserved alanine with glycine in each repeat to determine the distribution of structure in the transition state ensembles of constructs containing one (Nank1-5C1) and two consensus (

SUBMITTER: Tripp KW 

PROVIDER: S-EPMC2474552 | biostudies-literature | 2008 Apr

REPOSITORIES: biostudies-literature