The dual role of a loop with low loop contact distance in folding and domain swapping.

TitleThe dual role of a loop with low loop contact distance in folding and domain swapping.
Publication TypeJournal Article
Year of Publication2002
AuthorsLinhananta, A, Zhou H, Zhou Y
JournalProtein science : a publication of the Protein Society
Volume11
Pagination1695-701
Date Published2002 Jul
Abstract

Alpha helices, beta strands, and loops are the basic building blocks of protein structure. The folding kinetics of alpha helices and beta strands have been investigated extensively. However, little is known about the formation of loops. Experimental studies show that for some proteins, the formation of a single loop is the rate-determining step for folding, whereas for others, a loop (or turn) can misfold to serve as the hinge loop region for domain-swapped species. Computer simulations of an all-atom model of fragment B of Staphylococcal protein A found that the formation of a single loop initiates the dominant folding pathway. On the other hand, the stability analysis of intermediates suggests that the same loop is a likely candidate to serve as a hinge loop for domain swapping. To interpret the simulation result, we developed a simple structural parameter: the loop contact distance (LCD), or the sequence distance of contacting residues between a loop and the rest of the protein. The parameter is applied to a number of other proteins, including SH3 domains and prion protein. The results suggest that a locally interacting loop (low LCD) can either promote folding or serve as the hinge region for domain swapping. Thus, there is an intimate connection between folding and domain swapping, a possible cause of misfolding and aggregation.

Pub Med Link

http://www.ncbi.nlm.nih.gov/pubmed/12070322?dopt=Abstract

Alternate JournalProtein Sci.
Citekey12070322