The structure of a folding intermediate provides insight into differences in immunoglobulin amyloidogenicity.

ABSTRACT: Folding intermediates play a key role in defining protein folding and assembly pathways as well as those of misfolding and aggregation. Yet, due to their transient nature, they are poorly accessible to high-resolution techniques. Here, we made use of the intrinsically slow folding reaction of an antibody domain to characterize its major folding intermediate in detail. Furthermore, by a single point mutation we were able to trap the intermediate in equilibrium and characterize it at atomic resolution. The intermediate exhibits the basic beta-barrel topology, yet some strands are distorted. Surprisingly, two short strand-connecting helices conserved in constant antibody domains assume their completely native structure already in the intermediate, thus providing a scaffold for adjacent strand

SUBMITTER: Feige MJ 

PROVIDER: S-EPMC2533197 | biostudies-literature | 2008 Sep

REPOSITORIES: biostudies-literature