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 journalArticlepeer-review

43 Scopus citations


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
Issue number12
StatePublished - Jun 16 2010

ASJC Scopus subject areas

  • Biophysics


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