How a protein searches for its site on DNA: the mechanism of facilitated diffusion

Mirny, Leonid A.; Slutsky, Michael; Wunderlich, Zeba; Tafvizi, Anahita; Leith, Jason S.; Košmrlj, Andrej

doi:10.1088/1751-8113/42/43/434013

Cited by 358 publications

(602 citation statements)

References 53 publications

Supporting

Mentioning

564

Contrasting

Unclassified

Order By: Relevance

“…However, many details of the mechanisms of the protein search for targets on DNA still remain not well understood. [27][28][29][30][31] One of the most fascinating observations in this field is that many proteins can find and recognize their specific binding sites much faster than expected if the search would take place only via 3D bulk diffusion. 3,5,6,27,28 This surprising result is called a facilitated diffusion, and it is frequently argued that this happens due to the protein search being a combination of 3D and 1D modes.…”

Section: Introductionmentioning

confidence: 99%

“…3,5,6,27,28 This surprising result is called a facilitated diffusion, and it is frequently argued that this happens due to the protein search being a combination of 3D and 1D modes. 3,5,6,27,28 More specifically, the proposed picture assumes that the protein molecule associates non-specifically to DNA, scans some length of DNA by sliding, dissociates from DNA and repeats these actions several times until the target is located. Several experiments support this point of view.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

2015

View full text Add to dashboard Cite

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

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

2015

View full text Add to dashboard Cite

show abstract

“…In brief, the idea is to provide two different 1D sliding modes: a first, reading mode, where the protein is able to read the sequence with a reduced mobility, and a second, diffusing mode where the protein is able to move relatively rapidly along the double helix, but is essentially blind to the sequence [7,58,59,60]. The conformation change was initially attributed to a microscopic binding of the protein to the DNA accompanied by water and ion extrusion, but such a transition is usually accompanied by a large heat capacity change [61] that in turn need significant structural changes to be accounted for.…”

Section: Two-state Modelsmentioning

confidence: 99%

Protein–DNA Electrostatics

Barbi¹,

Paillusson²

2013

Dynamics of Proteins and Nucleic Acids

View full text Add to dashboard Cite

Gene expression and regulation rely on an apparently finely tuned set of reactions between some proteins and DNA. Such DNA-binding proteins have to find specific sequences on very long DNA molecules and they mostly do so in absence of any active process. It has been rapidly recognized that to achieve this task these proteins should be efficient at both searching (i.e. sampling fast relevant parts of DNA) and finding (i.e. recognizing the specific site).A two-mode search and variants of it have been suggested since the 70s to explain either a fast search or an efficient recognition. Combining these two properties at a phenomenological level is however more difficult as they appear to have antagonist roles. To overcome this difficulty, one may simply need to drop the dichotomic view inherent to the two-mode search and look more thoroughly at the set of interactions between DNA-binding proteins and a given 1 arXiv:1311.7496v1 [physics.bio-ph] 29 Nov 2013 DNA segment either specific or non-specific. This chapter demonstrates that, in doing so in a very generic way, one may indeed find a potential reconciliation between a fast search and an efficient recognition. Although a lot remains to be done, this could be the time for a change of paradigm.

show abstract

“…By now, it is well proven that the homology search is not an active process since ATP hydrolysis is not required to proceed forward (17,18). Therefore, it must be related to protein search for targets on DNA that have been intensively investigated in recent years (23)(24)(25)(26)(27)(28)(29)(30). However, a comprehensive description of the mechanisms of the homology search still does not exist even for simplified in vitro systems.…”

Section: Introductionmentioning

confidence: 99%

On the Mechanism of Homology Search by RecA Protein Filaments

Kochugaeva

Shvets

Kolomeisky

2017

Biophysical Journal

View full text Add to dashboard Cite

Genetic stability is a key factor in maintaining, survival and reproduction of biological cells. It relies on many processes, but one of the most important is a homologous recombination, in which the repair of breaks in double-stranded DNA molecules is taking place with a help of several specific proteins. In bacteria this task is accomplished by RecA proteins that are active as nucleoprotein filaments formed on single-stranded segments of DNA. A critical step in the homologous recombination is a search for a corresponding homologous region on DNA, which is called a homology search. Recent single-molecule experiments clarified some aspects of this process, but its molecular mechanisms remain not well understood. We developed a quantitative theoretical approach to analyze the homology search. It is based on a discrete-state stochastic model that takes into account the most relevant physical-chemical processes in the system. Using a method of first-passage processes, a full dynamic description of the homology search is presented. It is found that the search dynamics depends on the degree of extension of DNA molecules and on the size of RecA nucleoprotein filaments, in agreement with experimental single-molecule measurements of DNA pairing by RecA proteins. Our theoretical calculations, supported by extensive Monte Carlo computer simulations, provide a molecular description of the mechanisms of the homology search.

show abstract

How a protein searches for its site on DNA: the mechanism of facilitated diffusion

Cited by 358 publications

References 53 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

Protein–DNA Electrostatics

On the Mechanism of Homology Search by RecA Protein Filaments

Contact Info

Product

Resources

About