Segmentation and the Entropic Elasticity of Modular Proteins

TitleSegmentation and the Entropic Elasticity of Modular Proteins
Publication TypeJournal Article
Year of Publication2018
AuthorsBerkovich R, Fernandez VI, Stirnemann G, Valle-Orero J, Fernandez JM
JournalJ Phys Chem Lett
Volume9
Pagination4707-4713
Date PublishedAug
Abstract

Single-molecule force spectroscopy utilizes polyproteins, which are composed of tandem modular domains, to study their mechanical and structural properties. Under the application of external load, the polyproteins respond by unfolding and refolding domains to acquire the most favored extensibility. However, unlike single-domain proteins, the sequential unfolding of the each domain modifies the free energy landscape (FEL) of the polyprotein nonlinearly. Here we use force-clamp (FC) spectroscopy to measure unfolding and collapse-refolding dynamics of polyubiquitin and poly(I91). Their reconstructed unfolding FEL involves hundreds of kB T in accumulating work performed against conformational entropy, which dwarfs the ∼30 kB T that is typically required to overcome the free energy difference of unfolding. We speculate that the additional entropic energy caused by segmentation of the polyprotein to individual proteins plays a crucial role in defining the "shock absorber" properties of elastic proteins such as the giant muscle protein titin.

DOI10.1021/acs.jpclett.8b01925
Citation Key2018|2135
PubMed ID30058807