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Molecular mechanics of coiled coils loaded in the shear geometry.

ABSTRACT: Coiled coils are important nanomechanical building blocks in biological and biomimetic materials. A mechanistic molecular understanding of their structural response to mechanical load is essential for elucidating their role in tissues and for utilizing and tuning these building blocks in materials applications. Using a combination of single-molecule force spectroscopy (SMFS) and steered molecular dynamics (SMD) simulations, we have investigated the mechanics of synthetic heterodimeric coiled coils of different length (3-4 heptads) when loaded in shear geometry. Upon shearing, we observe an initial rise in the force, which is followed by a constant force plateau and ultimately strand separation. The force required for strand separation depends on the coiled coil length and the applied loading rate, suggesting that coiled coil shearing occurs out of equilibrium. This out-of-equilibrium behaviour is determined by a complex structural response which involves helix uncoiling, uncoiling-assisted sliding of the helices relative to each other in the direction of the applied force as well as uncoiling-assisted dissociation perpendicular to the force axis. These processes follow a hierarchy of timescales with helix uncoiling being faster than sliding and sliding being faster than dissociation. In SMFS experiments, strand separation is dominated by uncoiling-assisted dissociation and occurs at forces between 25-45 pN for the shortest 3-heptad coiled coil and between 35-50 pN for the longest 4-heptad coiled coil. These values are highly similar to the forces required for shearing apart short double-stranded DNA oligonucleotides, reinforcing the potential role of coiled coils as nanomechanical building blocks in applications where protein-based structures are desired.

SUBMITTER: Goktas M

PROVIDER: S-EPMC5969510 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Molecular mechanics of coiled coils loaded in the shear geometry.

Goktas Melis M Luo Chuanfu C Sullan Ruby May A RMA Bergues-Pupo Ana E AE Lipowsky Reinhard R Vila Verde Ana A Blank Kerstin G KG

Chemical science 20180423 20

Coiled coils are important nanomechanical building blocks in biological and biomimetic materials. A mechanistic molecular understanding of their structural response to mechanical load is essential for elucidating their role in tissues and for utilizing and tuning these building blocks in materials applications. Using a combination of single-molecule force spectroscopy (SMFS) and steered molecular dynamics (SMD) simulations, we have investigated the mechanics of synthetic heterodimeric coiled coi ...[more]

PMID: 29899954

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Project description:ARCIMBOLDO solves the phase problem by combining the location of small model fragments using Phaser with density modification and autotracing using SHELXE. Mainly helical structures constitute favourable cases, which can be solved using polyalanine helical fragments as search models. Nevertheless, the solution of coiled-coil structures is often complicated by their anisotropic diffraction and apparent translational noncrystallographic symmetry. Long, straight helices have internal translational symmetry and their alignment in preferential directions gives rise to systematic overlap of Patterson vectors. This situation has to be differentiated from the translational symmetry relating different monomers. ARCIMBOLDO_LITE has been run on single workstations on a test pool of 150 coiled-coil structures with 15-635 amino acids per asymmetric unit and with diffraction data resolutions of between 0.9 and 3.0 Å. The results have been used to identify and address specific issues when solving this class of structures using ARCIMBOLDO. Features from Phaser v.2.7 onwards are essential to correct anisotropy and produce translation solutions that will pass the packing filters. As the resolution becomes worse than 2.3 Å, the helix direction may be reversed in the placed fragments. Differentiation between true solutions and pseudo-solutions, in which helix fragments were correctly positioned but in a reverse orientation, was found to be problematic at resolutions worse than 2.3 Å. Therefore, after every new fragment-placement round, complete or sparse combinations of helices in alternative directions are generated and evaluated. The final solution is once again probed by helix reversal, refinement and extension. To conclude, density modification and SHELXE autotracing incorporating helical constraints is also exploited to extend the resolution limit in the case of coiled coils and to enhance the identification of correct solutions. This study resulted in a specialized mode within ARCIMBOLDO for the solution of coiled-coil structures, which overrides the resolution limit and can be invoked from the command line (keyword coiled_coil) or ARCIMBOLDO_LITE task interface in CCP4i.

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Molecular mechanics of coiled coils loaded in the shear geometry.

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Molecular mechanics of coiled coils loaded in the shear geometry.

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