Correlations within polyprotein forced unfolding dwell-times introduce sequential dependency

Einat Chetrit, Yasmine Meroz, Ziv Klausner, Ronen Berkovich*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Polyproteins, comprised from proteins arrayed in tandem, respond to mechanical loads through partial unfolding and extension. This response to tension that enables their physiological function is related to the ability to dynamically regulate their elasticity. The unique arrangement of their individual mechanical components (proteins and polymeric linkers), and the interactions between them eventually determines their performance. The sequential unfolding-times within a polyprotein are inherently assumed to be independent and identically distributed (iid), thus expected to follow an exponential distribution. Nevertheless, a large body of literature using single molecule force spectroscopy (SMFS) provides evidence that forced unfolding-times of N proteins within a polyprotein do not follow the exponential distribution. Here we use SMFS with Atomic Force Microscopy to measure the unfolding kinetics of Poly-(I91)8 at 180 pN. The unfolding time-intervals were statistically analysed using three common approaches, all exhibiting an N-effect: hierarchical behavior with non-identical unfolding time distributions. Using continuous time random walk approach indicates that the unfolding times display subdiffusive features. Put together with free-energy reconstruction of the whole unfolding polyprotein, we provide physical explanation for this nontrivial behavior, according to which the elongating polypeptide chain with each unfolding event intervenes with the sequential unfolding probabilities and correlates them.

Original languageEnglish
Article number107495
JournalJournal of Structural Biology
Volume210
Issue number3
DOIs
StatePublished - 1 Jun 2020

Funding

FundersFunder number
Israel Science Foundation152/11
Planning and Budgeting Committee of the Council for Higher Education of Israel

    Keywords

    • AFM
    • Correlations
    • Force-spectroscopy
    • Non-exponential kinetics
    • Polyprotein
    • Single-molecule

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