UNSTRUCTURED NASCENT-CHAIN SEGMENTS GENERATE PICONEWTONS OF FORCE THAT ARE TRANSMITTED THROUGH THE PEPTIDE BACKBONE TO THE RIBOSOME P-SITE
Open Access
Author:
Fritch, Ben R
Graduate Program:
Chemistry
Degree:
Master of Science
Document Type:
Master Thesis
Date of Defense:
April 15, 2017
Committee Members:
Dr. Edward O'Brien, Thesis Advisor/Co-Advisor Dr. Scott Showalter, Committee Member Dr. Gerald Knizia, Committee Member
Keywords:
Co-translational unstructured proteins force
Abstract:
Mechanical forces acting on the ribosome can alter the speed of protein
synthesis. These forces have diverse origins including the SecA motor protein that aids
in protein translocation, and co-translational protein folding, indicating that co
translational processes can regulate translation through the medium of
mechanochemistry. Using in situ experimental measurements of changes in nascent
chain extension in the exit tunnel, in conjunction with all-atom and coarse-grained
computer simulations, we demonstrate that when a nascent chain is lengthened, its
unstructured segments outside the ribosome exit tunnel can generate piconewtons of
force that is transmitted through the polypeptide backbone to the ribosome’s catalytic
core. Since all nascent protein segments start out as unfolded structural ensembles,
these results indicate that a universal pulling force is present during protein synthesis
that increases with increasing protein length.
