Dataset Information

Catch and Release DNA Decoys: Capture and Photochemical Dissociation of NF-?B Transcription Factors.

ABSTRACT: Catch and release DNA decoys (CRDDs) are a new class of non-natural DNA probes that capture and dissociate from DNA-binding proteins using a light trigger. Photolytic cleavage of non-natural nucleobases in the CRDD yields abasic sites and truncation products that lower the affinity of the CRDD for its protein target. Herein, we demonstrate the ability of the first-generation CRDD to bind and release NF-?B proteins. This platform technology should be applicable to other DNA-binding proteins by modification of the target sequence.

SUBMITTER: Struntz NB

PROVIDER: S-EPMC4941104 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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Catch and Release DNA Decoys: Capture and Photochemical Dissociation of NF-κB Transcription Factors.

Struntz Nicholas B NB Harki Daniel A DA

ACS chemical biology 20160407 6

Catch and release DNA decoys (CRDDs) are a new class of non-natural DNA probes that capture and dissociate from DNA-binding proteins using a light trigger. Photolytic cleavage of non-natural nucleobases in the CRDD yields abasic sites and truncation products that lower the affinity of the CRDD for its protein target. Herein, we demonstrate the ability of the first-generation CRDD to bind and release NF-κB proteins. This platform technology should be applicable to other DNA-binding proteins by mo ...[more]

PMID: 27054264

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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

Catch and Release DNA Decoys: Capture and Photochemical Dissociation of NF-?B Transcription Factors.

Publications

Catch and Release DNA Decoys: Capture and Photochemical Dissociation of NF-κB Transcription Factors.

Similar Datasets

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