TY - JOUR
T1 - Segmentation and the Entropic Elasticity of Modular Proteins
AU - Berkovich, Ronen
AU - Fernandez, Vicente I.
AU - Stirnemann, Guillaume
AU - Valle-Orero, Jessica
AU - Fernández, Julio M.
N1 - Publisher Copyright:
Copyright © 2018 American Chemical Society.
PY - 2018/8/16
Y1 - 2018/8/16
N2 - 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 kBT in accumulating work performed against conformational entropy, which dwarfs the ∼30kBT 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.
AB - 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 kBT in accumulating work performed against conformational entropy, which dwarfs the ∼30kBT 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.
UR - http://www.scopus.com/inward/record.url?scp=85051828419&partnerID=8YFLogxK
U2 - 10.1021/acs.jpclett.8b01925
DO - 10.1021/acs.jpclett.8b01925
M3 - Article
C2 - 30058807
AN - SCOPUS:85051828419
SN - 1948-7185
VL - 9
SP - 4707
EP - 4713
JO - Journal of Physical Chemistry Letters
JF - Journal of Physical Chemistry Letters
IS - 16
ER -