dorsal/arxiv
View SchemaKinetics of protein-DNA interaction: facilitated target location in sequence-dependent potential
| Authors | Michael Slutsky, Leonid A. Mirny |
|---|---|
| Categories | |
| ArXiv ID | q-bio/0402005 |
| URL | https://arxiv.org/abs/q-bio/0402005 |
| DOI | 10.1529/biophysj.104.050765 |
| Journal | Biophys. J. 87:4021-4035 (2004) |
Abstract
Recognition and binding of specific sites on DNA by proteins is central for many cellular functions such as transcription, replication, and recombination. In the process of recognition, a protein rapidly searches for its specific site on a long DNA molecule and then strongly binds this site. Here we aim to find a mechanism that can provide both a fast search (1-10 sec) and high stability of the specific protein-DNA complex ($K_d=10^{-15}-10^{-8}$ M). Earlier studies have suggested that rapid search involves the sliding of a protein along the DNA. Here we consider sliding as a one-dimensional (1D) diffusion in a sequence-dependent rough energy landscape. We demonstrate that, in spite of the landscape's roughness, rapid search can be achieved if 1D sliding is accompanied by 3D diffusion. We estimate the range of the specific and non-specific DNA-binding energy required for rapid search and suggest experiments that can test our mechanism. We show that optimal search requires a protein to spend half of time sliding along the DNA and half diffusing in 3D. We also establish that, paradoxically, realistic energy functions cannot provide both rapid search and strong binding of a rigid protein. To reconcile these two fundamental requirements we propose a search-and-fold mechanism that involves the coupling of protein binding and partial protein folding. Proposed mechanism has several important biological implications for search in the presence of other proteins and nucleosomes, simultaneous search by several proteins etc. Proposed mechanism also provides a new framework for interpretation of experimental and structural data on protein-DNA interactions.
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"abstract": "Recognition and binding of specific sites on DNA by proteins is central for\nmany cellular functions such as transcription, replication, and recombination.\nIn the process of recognition, a protein rapidly searches for its specific site\non a long DNA molecule and then strongly binds this site. Here we aim to find a\nmechanism that can provide both a fast search (1-10 sec) and high stability of\nthe specific protein-DNA complex ($K_d=10^{-15}-10^{-8}$ M).\n Earlier studies have suggested that rapid search involves the sliding of a\nprotein along the DNA. Here we consider sliding as a one-dimensional (1D)\ndiffusion in a sequence-dependent rough energy landscape. We demonstrate that,\nin spite of the landscape\u0027s roughness, rapid search can be achieved if 1D\nsliding is accompanied by 3D diffusion. We estimate the range of the specific\nand non-specific DNA-binding energy required for rapid search and suggest\nexperiments that can test our mechanism. We show that optimal search requires a\nprotein to spend half of time sliding along the DNA and half diffusing in 3D.\nWe also establish that, paradoxically, realistic energy functions cannot\nprovide both rapid search and strong binding of a rigid protein. To reconcile\nthese two fundamental requirements we propose a search-and-fold mechanism that\ninvolves the coupling of protein binding and partial protein folding.\n Proposed mechanism has several important biological implications for search\nin the presence of other proteins and nucleosomes, simultaneous search by\nseveral proteins etc. Proposed mechanism also provides a new framework for\ninterpretation of experimental and structural data on protein-DNA interactions.",
"arxiv_id": "q-bio/0402005",
"authors": [
"Michael Slutsky",
"Leonid A. Mirny"
],
"categories": [
"q-bio.BM",
"cond-mat.dis-nn",
"physics.bio-ph"
],
"doi": "10.1529/biophysj.104.050765",
"journal_ref": "Biophys. J. 87:4021-4035 (2004)",
"title": "Kinetics of protein-DNA interaction: facilitated target location in sequence-dependent potential",
"url": "https://arxiv.org/abs/q-bio/0402005"
},
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