Mechanical unfolding of alpha- and beta-helical protein motifs

Elizabeth P. Debenedictis, Sinan Keten*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

Alpha-helices and beta-sheets are the two most common secondary structure motifs in proteins. Beta-helical structures merge features of the two motifs, containing two or three beta-sheet faces connected by loops or turns in a single protein. Beta-helical structures form the basis of proteins with diverse mechanical functions such as bacterial adhesins, phage cell-puncture devices, antifreeze proteins, and extracellular matrices. Alpha-helices are commonly found in cellular and extracellular matrix components, whereas beta-helices such as curli fibrils are more common as bacterial and biofilm matrix components. It is currently not known whether it may be advantageous to use one helical motif over the other for different structural and mechanical functions. To better understand the mechanical implications of using different helix motifs in networks, here we use Steered Molecular Dynamics (SMD) simulations to mechanically unfold multiple alpha- and beta-helical proteins at constant velocity at the single molecule scale. We focus on the energy dissipated during unfolding as a means of comparison between proteins and work normalized by protein characteristics (initial and final length, # H-bonds, # residues, etc.). We find that although alpha-helices such as keratin and beta-helices CsgA and CsgB can require similar amounts of work to unfold, the normalized work per hydrogen bond, initial end to end length, and number of residues is greater for beta-helices at the same pulling rate. To explain this, we analyze the orientation of the backbone alpha carbons and backbone hydrogen bonds during unfolding. We find that the larger width and shorter height of beta-helices results in smaller angles between the protein backbone and the pulling direction during unfolding. As subsequent strands are separated from the beta-helix core, the angle between the backbone and the pulling direction diminishes. This marks a transition where beta-sheet hydrogen bonds become loaded predominantly in a collective shearing mode, which requires a larger rupture force. This finding underlines the importance of geometry in optimizing resistance to mechanical unfolding in proteins. The helix radius is identified here as an important parameter that governs how much sacrificial energy dissipation capacity can be stored in protein networks, where beta-helices offer unique properties.

Original languageEnglish (US)
Pages (from-to)1243-1252
Number of pages10
JournalSoft Matter
Volume15
Issue number6
DOIs
StatePublished - 2019

Funding

The authors acknowledge a supercomputing grant from the Northwestern University High Performance Computing Center and the Department of Defense Supercomputing Resource Center. E. P. D. gratefully acknowledges support from the Ryan Fellowship and the Northwestern University International Institute for Nanotechnology. This research was sponsored by an award from the Office of Naval Research Young Investigator Program (grant #N00014-15-1-2701). E. P. D. was additionally sponsored with Government support under and awarded by DoD, Air Force Office of Scientific Research, National Defense Science and Engineering Graduate (NDSEG) Fellowship, 32 CFR 168a. Elizabeth DeBenedictis is a doctoral graduate student in the department of Mechanical Engineering at Northwestern University. She began at Northwestern University in 2014 after obtaining her BS in Mechanical Engineering from the University of Cincinnati. Her current research is focused on uncovering the mechanics of proteinaceous biofilm components using computational techniques. She is supported by the International Institution of Nanotechnology at Northwestern University through the Ryan Fellowship and by the Department of Defense through the National Defense Science and Engineering Graduate Fellowship.

ASJC Scopus subject areas

  • General Chemistry
  • Condensed Matter Physics

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