Dataset Information

Phenomenological and microscopic theories for catch bonds.

ABSTRACT: Lifetimes of bound states of protein complexes or biomolecule folded states typically decrease when subject to mechanical force. However, a plethora of biological systems exhibit the counter-intuitive phenomenon of catch bonding, where non-covalent bonds become stronger under externally applied forces. The quest to understand the origin of catch-bond behavior has led to the development of phenomenological and microscopic theories that can quantitatively recapitulate experimental data. Here, we assess the successes and limitations of such theories in explaining experimental data. The most widely applied approach is a phenomenological two-state model, which fits all of the available data on a variety of complexes: actomyosin, kinetochore-microtubule, selectin-ligand, and cadherin-catenin binding to filamentous actin. With a primary focus on the selectin family of cell-adhesion complexes, we discuss the positives and negatives of phenomenological models and the importance of evaluating the physical relevance of fitting parameters. We describe a microscopic theory for selectins, which provides a structural basis for catch bonds and predicts a crucial allosteric role for residues Asn82-Glu88. We emphasize the need for new theories and simulations that can mimic experimental conditions, given the complex response of cell adhesion complexes to force and their potential role in a variety of biological contexts.

SUBMITTER: Chakrabarti S

PROVIDER: S-EPMC5580263 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Phenomenological and microscopic theories for catch bonds.

Chakrabarti Shaon S Hinczewski Michael M Thirumalai D D

Journal of structural biology 20160401 1

Lifetimes of bound states of protein complexes or biomolecule folded states typically decrease when subject to mechanical force. However, a plethora of biological systems exhibit the counter-intuitive phenomenon of catch bonding, where non-covalent bonds become stronger under externally applied forces. The quest to understand the origin of catch-bond behavior has led to the development of phenomenological and microscopic theories that can quantitatively recapitulate experimental data. Here, we a ...[more]

PMID: 27046010

Similar Datasets

Project description:Cellular structures are continually subjected to forces, which may serve as mechanical signals for cells through their effects on biomolecule interaction kinetics. Typically, molecular complexes interact via "slip bonds," so applied forces accelerate off rates by reducing transition energy barriers. However, biomolecules with multiple dissociation pathways may have considerably more complicated force dependencies. This is the case for DNA-binding proteins that undergo "facilitated dissociation," in which competitor biomolecules from solution enhance molecular dissociation in a concentration-dependent manner. Using simulations and theory, we develop a generic model that shows that proteins undergoing facilitated dissociation can form an alternative type of molecular bond, known as a "catch bond," for which applied forces suppress protein dissociation. This occurs because the binding by protein competitors responsible for the facilitated dissociation pathway can be inhibited by applied forces. Within the model, we explore how the force dependence of dissociation is regulated by intrinsic factors, including molecular sensitivity to force and binding geometry and the extrinsic factor of competitor protein concentration. We find that catch bonds generically emerge when the force dependence of the facilitated unbinding pathway is stronger than that of the spontaneous unbinding pathway. The sharpness of the transition between slip- and catch-bond kinetics depends on the degree to which the protein bends its DNA substrate. This force-dependent kinetics is broadly regulated by the concentration of competitor biomolecules in solution. Thus, the observed catch bond is mechanistically distinct from other known physiological catch bonds because it requires an extrinsic factor-competitor proteins-rather than a specific intrinsic molecular structure. We hypothesize that this mechanism for regulating force-dependent protein dissociation may be used by cells to modulate protein exchange, regulate transcription, and facilitate diffusive search processes.

Dataset Information

Phenomenological and microscopic theories for catch bonds.

Publications

Phenomenological and microscopic theories for catch bonds.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets