Nanomechanical properties of steric zipper globular structures

Neta Lester-Zer, Mnar Ghrayeb, Liraz Chai*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

The term amyloid defines a group of proteins that aggregate into plaques or fibers. Amyloid fibers gained their fame mostly due to their relation with neurodegenerative diseases in humans. However, secreted by lower organisms, such as bacteria and fungi, amyloid fibers play a functional role: for example, when they serve as cement in the extracellular matrix of biofilms. Originating either in humans or in microorganisms, the sequence of amyloid proteins is decorated with hexapeptides with high propensity to form fibers, known as steric zippers. We have found that steric zippers form globular structures on route to making fibers and exhibit a characteristic force–distance (F-D) fingerprint when pulled with an atomic force microscope (AFM) tip. Particularly, the F-D pulling curves showed force plateau steps, suggesting that the globular structures were composed of chains that were unwound like a yarn ball. Force plateau analysis showed that the F-D characteristic parameters were sequence sensitive, representing differences in the packing of the hexapeptides within the globules. These unprecedented findings show that steric zippers exhibit a characteristic nanomechanical signature in solution in addition to previously observed characteristic crystallographic structure. Getting to the fundamental interactions that govern the unzipping of full-length amyloid fibers may initiate the development of antiamyloid methods that target the physical in addition to the structural properties of steric zippers.

Original languageAmerican English
Pages (from-to)22478-22484
Number of pages7
JournalProceedings of the National Academy of Sciences of the United States of America
Volume116
Issue number45
DOIs
StatePublished - 5 Nov 2019

Bibliographical note

Publisher Copyright:
© 2019 National Academy of Sciences. All rights reserved.

Keywords

  • Amyloid proteins
  • Atomic force microscopy
  • Force spectroscopy
  • Single-molecule
  • Steric zippers

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