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High-force catch bonds between the Staphylococcus aureus surface protein SdrE and complement regulator factor H drive immune evasion.

ABSTRACT: The invasive bacterial pathogen Staphylococcus aureus recruits the complement regulatory protein factor H (fH) to its surface to evade the human immune system. Here, we report the identification of an extremely high-force catch bond used by the S. aureus surface protein SdrE to efficiently capture fH under mechanical stress. We find that increasing the external force applied to the SdrE-fH complex prolongs the lifetime of the bond at an extraordinary high force, 1,400 pN, above which the bond lifetime decreases as an ordinary slip bond. This catch-bond behavior originates from a variation of the dock, lock and latch interaction, where the SdrE ligand binding domains undergo conformational changes under stress, enabling the formation of long-lived hydrogen bonds with fH. The binding mechanism dissected here represents a potential target for new therapeutics against multidrug-resistant S. aureus strains.

SUBMITTER: Paiva TO

PROVIDER: S-EPMC10030832 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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High-force catch bonds between the Staphylococcus aureus surface protein SdrE and complement regulator factor H drive immune evasion.

Paiva Telmo O TO Geoghegan Joan A JA Dufrêne Yves F YF

Communications biology 20230321 1

The invasive bacterial pathogen Staphylococcus aureus recruits the complement regulatory protein factor H (fH) to its surface to evade the human immune system. Here, we report the identification of an extremely high-force catch bond used by the S. aureus surface protein SdrE to efficiently capture fH under mechanical stress. We find that increasing the external force applied to the SdrE-fH complex prolongs the lifetime of the bond at an extraordinary high force, 1,400 pN, above which the bond li ...[more]

PMID: 36944849

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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

High-force catch bonds between the Staphylococcus aureus surface protein SdrE and complement regulator factor H drive immune evasion.

Publications

High-force catch bonds between the Staphylococcus aureus surface protein SdrE and complement regulator factor H drive immune evasion.

Similar Datasets

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