title: Fast and forceful refolding of stretched alpha-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, beta-catenin, and clathrin, which are representative examples of over 800 predicted human proteins composed of tightly packed alpha-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.
authors.affiliation: Department of Mechanical Engineering and Materials Science, Center for Biologically Inspired Materials and Material Systems, Duke University, Durham, North Carolina, USA.
authors.forename: Minkyu
authors.initials: M
authors.lastname: Kim
authors.forename: Khadar
authors.initials: K
authors.lastname: Abdi
authors.forename: Gwangrog
authors.initials: G
authors.lastname: Lee
authors.forename: Mahir
authors.initials: M
authors.lastname: Rabbi
authors.forename: Whasil
authors.initials: W
authors.lastname: Lee
authors.forename: Ming
authors.initials: M
authors.lastname: Yang
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Schofield
authors.forename: Vann
authors.initials: V
authors.lastname: Bennett
authors.forename: Piotr E
authors.initials: PE
authors.lastname: Marszalek
mesh_terms: D001696:Biomechanical Phenomena; D006801:Humans; D007700:Kinetics; D018625:Microscopy, Atomic Force; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D011489:Protein Denaturation; D017510:Protein Folding; D020673:Protein Renaturation; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*; D013816:Thermodynamics
chemical_list: D010455:Peptides; D011506:Proteins