Fast and forceful refolding of stretched α-helical solenoid proteins

Minkyu Kim, Khadar Abdi, Gwangrog Lee, Mahir Rabbi, Whasil Lee, Ming Yang, Christopher J. Schofield, Vann Bennett, Piotr E. Marszalek

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Anfinsen's thermodynamic hypothesis implies that proteins can encode for stretching through reversible loss of structure. However, large in vitro extensions of proteins that occur through a progressive unfolding of their domains typically dissipate a significant amount of energy, and therefore are not thermodynamically reversible. Some coiled-coil proteins have been found to stretch nearly reversibly, although their extension is typically limited to 2.5 times their folded length. Here, we report investigations on the mechanical properties of individual molecules of ankyrin-R, β-catenin, and clathrin, which are representative examples of over 800 predicted human proteins composed of tightly packed α-helical repeats (termed ANK, ARM, or HEAT repeats, respectively) that form spiral-shaped protein domains. Using atomic force spectroscopy, we find that these polypeptides possess unprecedented stretch ratios on the order of 10-15, exceeding that of other proteins studied so far, and their extension and relaxation occurs with minimal energy dissipation. Their sequence-encoded elasticity is governed by stepwise unfolding of small repeats, which upon relaxation of the stretching force rapidly and forcefully refold, minimizing the hysteresis between the stretching and relaxing parts of the cycle. Thus, we identify a new class of proteins that behave as highly reversible nanosprings that have the potential to function as mechanosensors in cells and as building blocks in springy nanostructures. Our physical view of the protein component of cells as being comprised of predominantly inextensible structural elements under tension may need revision to incorporate springs.

Original languageEnglish (US)
Pages (from-to)3086-3092
Number of pages7
JournalBiophysical Journal
Volume98
Issue number12
DOIs
StatePublished - Jun 16 2010
Externally publishedYes

Fingerprint

Proteins
Ankyrin Repeat
Ankyrins
Catenins
Clathrin
Nanostructures
Elasticity
Cellular Structures
Thermodynamics
Spectrum Analysis
Peptides
In Vitro Techniques
Protein Domains

ASJC Scopus subject areas

  • Biophysics

Cite this

Kim, M., Abdi, K., Lee, G., Rabbi, M., Lee, W., Yang, M., ... Marszalek, P. E. (2010). Fast and forceful refolding of stretched α-helical solenoid proteins. Biophysical Journal, 98(12), 3086-3092. https://doi.org/10.1016/j.bpj.2010.02.054

Fast and forceful refolding of stretched α-helical solenoid proteins. / Kim, Minkyu; Abdi, Khadar; Lee, Gwangrog; Rabbi, Mahir; Lee, Whasil; Yang, Ming; Schofield, Christopher J.; Bennett, Vann; Marszalek, Piotr E.

In: Biophysical Journal, Vol. 98, No. 12, 16.06.2010, p. 3086-3092.

Research output: Contribution to journalArticle

Kim, M, Abdi, K, Lee, G, Rabbi, M, Lee, W, Yang, M, Schofield, CJ, Bennett, V & Marszalek, PE 2010, 'Fast and forceful refolding of stretched α-helical solenoid proteins', Biophysical Journal, vol. 98, no. 12, pp. 3086-3092. https://doi.org/10.1016/j.bpj.2010.02.054
Kim, Minkyu ; Abdi, Khadar ; Lee, Gwangrog ; Rabbi, Mahir ; Lee, Whasil ; Yang, Ming ; Schofield, Christopher J. ; Bennett, Vann ; Marszalek, Piotr E. / Fast and forceful refolding of stretched α-helical solenoid proteins. In: Biophysical Journal. 2010 ; Vol. 98, No. 12. pp. 3086-3092.
@article{e78361f0550e44898bd33b1f177b65da,
title = "Fast and forceful refolding of stretched α-helical solenoid proteins",
abstract = "Anfinsen's thermodynamic hypothesis implies that proteins can encode for stretching through reversible loss of structure. However, large in vitro extensions of proteins that occur through a progressive unfolding of their domains typically dissipate a significant amount of energy, and therefore are not thermodynamically reversible. Some coiled-coil proteins have been found to stretch nearly reversibly, although their extension is typically limited to 2.5 times their folded length. Here, we report investigations on the mechanical properties of individual molecules of ankyrin-R, β-catenin, and clathrin, which are representative examples of over 800 predicted human proteins composed of tightly packed α-helical repeats (termed ANK, ARM, or HEAT repeats, respectively) that form spiral-shaped protein domains. Using atomic force spectroscopy, we find that these polypeptides possess unprecedented stretch ratios on the order of 10-15, exceeding that of other proteins studied so far, and their extension and relaxation occurs with minimal energy dissipation. Their sequence-encoded elasticity is governed by stepwise unfolding of small repeats, which upon relaxation of the stretching force rapidly and forcefully refold, minimizing the hysteresis between the stretching and relaxing parts of the cycle. Thus, we identify a new class of proteins that behave as highly reversible nanosprings that have the potential to function as mechanosensors in cells and as building blocks in springy nanostructures. Our physical view of the protein component of cells as being comprised of predominantly inextensible structural elements under tension may need revision to incorporate springs.",
author = "Minkyu Kim and Khadar Abdi and Gwangrog Lee and Mahir Rabbi and Whasil Lee and Ming Yang and Schofield, {Christopher J.} and Vann Bennett and Marszalek, {Piotr E.}",
year = "2010",
month = "6",
day = "16",
doi = "10.1016/j.bpj.2010.02.054",
language = "English (US)",
volume = "98",
pages = "3086--3092",
journal = "Biophysical Journal",
issn = "0006-3495",
publisher = "Biophysical Society",
number = "12",

}

TY - JOUR

T1 - Fast and forceful refolding of stretched α-helical solenoid proteins

AU - Kim, Minkyu

AU - Abdi, Khadar

AU - Lee, Gwangrog

AU - Rabbi, Mahir

AU - Lee, Whasil

AU - Yang, Ming

AU - Schofield, Christopher J.

AU - Bennett, Vann

AU - Marszalek, Piotr E.

PY - 2010/6/16

Y1 - 2010/6/16

N2 - Anfinsen's thermodynamic hypothesis implies that proteins can encode for stretching through reversible loss of structure. However, large in vitro extensions of proteins that occur through a progressive unfolding of their domains typically dissipate a significant amount of energy, and therefore are not thermodynamically reversible. Some coiled-coil proteins have been found to stretch nearly reversibly, although their extension is typically limited to 2.5 times their folded length. Here, we report investigations on the mechanical properties of individual molecules of ankyrin-R, β-catenin, and clathrin, which are representative examples of over 800 predicted human proteins composed of tightly packed α-helical repeats (termed ANK, ARM, or HEAT repeats, respectively) that form spiral-shaped protein domains. Using atomic force spectroscopy, we find that these polypeptides possess unprecedented stretch ratios on the order of 10-15, exceeding that of other proteins studied so far, and their extension and relaxation occurs with minimal energy dissipation. Their sequence-encoded elasticity is governed by stepwise unfolding of small repeats, which upon relaxation of the stretching force rapidly and forcefully refold, minimizing the hysteresis between the stretching and relaxing parts of the cycle. Thus, we identify a new class of proteins that behave as highly reversible nanosprings that have the potential to function as mechanosensors in cells and as building blocks in springy nanostructures. Our physical view of the protein component of cells as being comprised of predominantly inextensible structural elements under tension may need revision to incorporate springs.

AB - Anfinsen's thermodynamic hypothesis implies that proteins can encode for stretching through reversible loss of structure. However, large in vitro extensions of proteins that occur through a progressive unfolding of their domains typically dissipate a significant amount of energy, and therefore are not thermodynamically reversible. Some coiled-coil proteins have been found to stretch nearly reversibly, although their extension is typically limited to 2.5 times their folded length. Here, we report investigations on the mechanical properties of individual molecules of ankyrin-R, β-catenin, and clathrin, which are representative examples of over 800 predicted human proteins composed of tightly packed α-helical repeats (termed ANK, ARM, or HEAT repeats, respectively) that form spiral-shaped protein domains. Using atomic force spectroscopy, we find that these polypeptides possess unprecedented stretch ratios on the order of 10-15, exceeding that of other proteins studied so far, and their extension and relaxation occurs with minimal energy dissipation. Their sequence-encoded elasticity is governed by stepwise unfolding of small repeats, which upon relaxation of the stretching force rapidly and forcefully refold, minimizing the hysteresis between the stretching and relaxing parts of the cycle. Thus, we identify a new class of proteins that behave as highly reversible nanosprings that have the potential to function as mechanosensors in cells and as building blocks in springy nanostructures. Our physical view of the protein component of cells as being comprised of predominantly inextensible structural elements under tension may need revision to incorporate springs.

UR - http://www.scopus.com/inward/record.url?scp=77953578930&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77953578930&partnerID=8YFLogxK

U2 - 10.1016/j.bpj.2010.02.054

DO - 10.1016/j.bpj.2010.02.054

M3 - Article

C2 - 20550922

AN - SCOPUS:77953578930

VL - 98

SP - 3086

EP - 3092

JO - Biophysical Journal

JF - Biophysical Journal

SN - 0006-3495

IS - 12

ER -