BstYI Bound to Noncognate DNA Reveals a “Hemispecific” Complex: Implications for DNA Scanning

Townson, Sharon A.; Samuelson, James C.; Bao, Yongming; Xu, Shuang-yong; Aggarwal, Aneel K.

doi:10.1016/j.str.2007.03.002

Cited by 30 publications

(40 citation statements)

References 43 publications

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“…Indeed, in real systems there are many sequences that have structures and chemical compositions similar to the specific sites. 20,33 The protein molecule can be trapped in these semispecific sites for large periods of time, and it is not clear then how the fast search can be accomplished. However, the majority of theoretical models for the facilitated diffusion ignore this effect, assuming that the nonspecifically bound proteins slide along the homogeneous DNA chain with the same diffusion constant.…”

Section: Introductionmentioning

confidence: 99%

Dynamics of the Protein Search for Targets on DNA in the Presence of Traps

2015

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Protein search for specific binding sites on DNA is a fundamental biological phenomenon associated with the beginning of most major biological processes. It is frequently found that proteins find and recognize their specific targets quickly and efficiently despite the complex nature of protein-DNA interactions in living cells. Although significant experimental and theoretical efforts was made in recent years, the mechanisms of these processes remain not well clarified. We present a theoretical study of the protein target search dynamics in the presence of semi-specific binding sites which are viewed as traps. Our theoretical approach employs a discrete-state stochastic method that accounts for the most important physical and chemical processes in the system. It also leads to a full analytical description for all dynamic properties of the protein search. It is found that the presence of traps can significantly modify the protein search dynamics. This effect depends on the spatial positions of the targets and traps, on distances between them, on the average sliding length of the protein along the DNA, and on the total length of DNA. Theoretical predictions are discussed using simple physical-chemical arguments, and they are also validated with extensive Monte Carlo computer simulations.keywords: protein-DNA interactions, discrete-state stochastic models, first-passage processes 2

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Section: Introductionmentioning

confidence: 99%

Dynamics of the Protein Search for Targets on DNA in the Presence of Traps

2015

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“…It has been found that proteins contact the DNA using approximately the same binding site and orientation in all complexes (10)(11)(12)(13)(14)(15)(16)(17)(18). In nonspecific complexes, the interface between the two molecules is stabilized by electrostatic interactions between charged protein side chains and the DNA backbone (1,(9)(10)(11)(12)(13)(14)(15)(16)(17).…”

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confidence: 99%

“…The kinetics of DNA sequence recognition (3,4) often involve multistate kinetic routes with populated intermediates (4)(5)(6)(7)(8). The build up of molecular interactions along multistate routes has been deduced indirectly from structural and thermodynamic studies (1)(2)(3)(9)(10)(11)(12)(13)(14)(15)(16)(17), but kinetic characterization of intermediates and transition state ensembles is still scarce.…”

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confidence: 99%

“…The structures of several proteins in complex with target DNA sites, variants thereof and random DNA sequences, have been solved and used as models for transient intermediates of specific recognition (10)(11)(12)(13)(14)(15)(16)(17). It has been found that proteins contact the DNA using approximately the same binding site and orientation in all complexes (10)(11)(12)(13)(14)(15)(16)(17)(18).…”

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confidence: 99%

“…In nonspecific complexes, the interface between the two molecules is stabilized by electrostatic interactions between charged protein side chains and the DNA backbone (1,(9)(10)(11)(12)(13)(14)(15)(16)(17). In complexes with target DNA sites, there are also interactions between side chains and bases (10)(11)(12)(13)(14)(15)(16)(17). Strikingly, some so-called "dual-role residues" interact with the DNA backbone in nonspecific complexes and with DNA bases in specific complexes (14,15,17) or form different interactions with bases in nonspecific and specific complexes (13).…”

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Experimental snapshots of a protein-DNA binding landscape

Sánchez

Ferreiro

Dellarole

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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Protein recognition of DNA sites is a primary event for gene function. Its ultimate mechanistic understanding requires an integrated structural, dynamic, kinetic, and thermodynamic dissection that is currently limited considering the hundreds of structures of protein-DNA complexes available. We describe a protein-DNA-binding pathway in which an initial, diffuse, transition state ensemble with some nonnative contacts is followed by formation of extensive nonnative interactions that drive the system into a kinetic trap. Finally, nonnative contacts are slowly rearranged into native-like interactions with the DNA backbone. Dissimilar protein-DNA interfaces that populate along the DNA-binding route are explained by a temporary degeneracy of protein-DNA interactions, centered on "dual-role" residues. The nonnative species slow down the reaction allowing for extended functionality.energy landscape | human papillomavirus E2 protein | kinetic trap | kinetics | protein-DNA interaction

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Conformational changes in DNA‐binding proteins: Relationships with precomplex features and contributions to specificity and stability

2013

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Both Proteins and DNA undergo conformational changes in order to form functional complexes and also to facilitate interactions with other molecules. These changes have direct implications for the stability and specificity of the complex, as well as the cooperativity of interactions between multiple entities. In this work, we have extensively analyzed conformational changes in DNA-binding proteins by superimposing DNA-bound and unbound pairs of protein structures in a curated database of 90 proteins. We manually examined each of these pairs, unified the authors' annotations, and summarized our observations by classifying conformational changes into six structural categories. We explored a relationship between conformational changes and functional classes, binding motifs, target specificity, biophysical features of unbound proteins, and stability of the complex. In addition, we have also investigated the degree to which the intrinsic flexibility can explain conformational changes in a subset of 52 proteins with high quality coordinate data. Our results indicate that conformational changes in DNA-binding proteins contribute significantly to both the stability of the complex and the specificity of targets recognized by them. We also conclude that most conformational changes occur in proteins interacting with specific DNA targets, even though unbound protein structures may have sufficient information to interact with DNA in a nonspecific manner.Proteins 2014; 82:841-857.

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BstYI Bound to Noncognate DNA Reveals a “Hemispecific” Complex: Implications for DNA Scanning

Cited by 30 publications

References 43 publications

Dynamics of the Protein Search for Targets on DNA in the Presence of Traps

Dynamics of the Protein Search for Targets on DNA in the Presence of Traps

Experimental snapshots of a protein-DNA binding landscape

Conformational changes in DNA‐binding proteins: Relationships with precomplex features and contributions to specificity and stability

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