DNA結合蛋白

DNA結合蛋白（DNA-binding protein）是指能透過DNA結合結構域（英語：DNA-binding domain）（DBD）與單股或雙股DNA結合的一類蛋白質^[1]^[2]^[3]。一般來說，能與特異DNA序列結合的DNA結合蛋白主要經由與B-DNA（生物體內DNA一般都是B-DNA形式）的大溝結合來識別DNA序列。因為B-DNA的大溝區域能容許更多蛋白質上的官能基靠近並與之進行相互作用^[4]^[5]。

蛋白質與DNA的相互作用

蛋白質與DNA的結合受到pH值、溫度、離子強度、電場，以及大分子擁擠（英語：Macromolecular crowding）等多種條件的影響，具體分為特異性與非特異性兩種。非特異性的結合指蛋白質與DNA的結合不依賴特測序列，而特異性的結合則只會發生在特定的DNA序列上^[6]^[7]。在Cas9/CRSIPER系統出現前作為主流基因編輯工具的鋅指蛋白以及TALENs都是依賴特異性的DNA蛋白間結合工作的^[8]。

檢測方法

較早期的檢測蛋白與DNA間相互作用的方法^[9]包括凝膠遷移實驗（EMSA）^[10]^[11]、DNA-蛋白質相互作用ELISA實驗（DPI-ELISA）^[12]、DNA酶足跡法（英語：DNase footprinting assay）（DNase footprinting assay） ^[13]等等。而染色質免疫沉澱法（ChIP）則是目前較為通行的檢測體內DNA與蛋白質相互作用的方法^[14]。

非特異性DNA結合蛋白

最常見的一種非特異性DNA結合蛋白是真核生物染色質中與DNA結合的組蛋白。組蛋白主要是通過所帶的正電荷與帶負電的DNA結合，所以組蛋白與DNA之間的結合不依賴DNA上的特測序列。這也符合組蛋白的生物學功能，因為組蛋白需要與各種不同的DNA片段結合形成染色質的基本組成單位核小體^[15]^[16]。另外，真核生物染色質上能夠使DNA鏈發生彎曲的高遷移率族（HMG）蛋白與DNA之間的結合也是非特異性的^[17]^[18]^[19]。

特異性DNA結合蛋白

很多特異性DNA結合蛋白屬於轉錄因子。轉錄因子依賴其特有的DNA結合結構域與DNA上的特測序列結合。一般來說，轉錄因子在與DNA結合後，會招募酶對DNA或組蛋白進行修飾，進而調控基因的表達水平^[20]^[21]。

參見

參考文獻

^ Travers, A. A. DNA-protein interactions. London: Springer. 1993. ISBN 978-0-412-25990-6.
^ Pabo CO, Sauer RT. Protein-DNA recognition. Annu. Rev. Biochem. 1984, 53 (1): 293–321. PMID 6236744. doi:10.1146/annurev.bi.53.070184.001453.
^ Dickerson R.E. The DNA helix and how it is read. Sci Am. 1983, 249 (6): 94–111. Bibcode:1983SciAm.249f..94D. doi:10.1038/scientificamerican1283-94.
^ Zimmer C, Wähnert U. Nonintercalating DNA-binding ligands: specificity of the interaction and their use as tools in biophysical, biochemical and biological investigations of the genetic material. Prog. Biophys. Mol. Biol. 1986, 47 (1): 31–112. PMID 2422697. doi:10.1016/0079-6107(86)90005-2 .
^ Dervan PB. Design of sequence-specific DNA-binding molecules. Science. April 1986, 232 (4749): 464–71. Bibcode:1986Sci...232..464D. PMID 2421408. doi:10.1126/science.2421408.
^ Bewley CA, Gronenborn AM, Clore GM. Minor groove-binding architectural proteins: structure, function, and DNA recognition. Annu Rev Biophys Biomol Struct. 1998, 27: 105–31. PMC 4781445 . PMID 9646864. doi:10.1146/annurev.biophys.27.1.105.
^ Ganji, Mahipal; Docter, Margreet; Le Grice, Stuart F. J.; Abbondanzieri, Elio A. DNA binding proteins explore multiple local configurations during docking via rapid rebinding. Nucleic Acids Research. 2016-09-30, 44 (17): 8376–8384. ISSN 0305-1048. PMC 5041478 . PMID 27471033. doi:10.1093/nar/gkw666.
^ Clark KJ, Voytas DF, Ekker SC. A TALE of two nucleases: gene targeting for the masses?. Zebrafish. September 2011, 8 (3): 147–9. PMC 3174730 . PMID 21929364. doi:10.1089/zeb.2011.9993.
^ Cai YH, Huang H. Advances in the study of protein–DNA interaction. Amino Acids. July 2012, 43 (3): 1141–6. PMID 22842750. S2CID 310256. doi:10.1007/s00726-012-1377-9.
^ Fried M, Crothers DM. Equilibria and kinetics of lac repressor-operator interactions by polyacrylamide gel electrophoresis. Nucleic Acids Res. 1981, 9 (23): 6505–6525. PMC 327619 . PMID 6275366. doi:10.1093/nar/9.23.6505.
^ Garner MM, Revzin A. A gel electrophoresis method for quantifying the binding of proteins to specific DNA regions: application to components of the Escherichia coli lactose operon regulatory system. Nucleic Acids Res. 1981, 9 (13): 3047–3060. PMC 327330 . PMID 6269071. doi:10.1093/nar/9.13.3047.
^ Brand LH, Kirchler T, Hummel S, Chaban C, Wanke D. DPI-ELISA: a fast and versatile method to specify the binding of plant transcription factors to DNA in vitro.. Plant Methods. 2010, 25 (6): 25. PMC 3003642 . PMID 21108821. doi:10.1186/1746-4811-6-25 .
^ Galas DJ, Schmitz A. DNAse footprinting: a simple method for the detection of protein-DNA binding specificity. Nucleic Acids Res. 1978, 5 (9): 3157–3170. PMC 342238 . PMID 212715. doi:10.1093/nar/5.9.3157.
^ Collas, Philippe. The Current State of Chromatin Immunoprecipitation. Molecular Biotechnology. January 2010, 45 (1): 87–100. PMID 20077036. doi:10.1007/s12033-009-9239-8.
^ Luger K, Mäder A, Richmond R, Sargent D, Richmond T. Crystal structure of the nucleosome core particle at 2.8 A resolution. Nature. 1997, 389 (6648): 251–60. Bibcode:1997Natur.389..251L. PMID 9305837. S2CID 4328827. doi:10.1038/38444.
^ Jenuwein T, Allis C. Translating the histone code. Science. 2001, 293 (5532): 1074–80. CiteSeerX 10.1.1.453.900 . PMID 11498575. S2CID 1883924. doi:10.1126/science.1063127.
^ Thomas J. HMG1 and 2: architectural DNA-binding proteins. Biochem Soc Trans. 2001, 29 (Pt 4): 395–401. PMID 11497996. doi:10.1042/BST0290395.
^ Murugesapillai, Divakaran; McCauley, Micah J.; Huo, Ran; Nelson Holte, Molly H.; Stepanyants, Armen; Maher, L. James; Israeloff, Nathan E.; Williams, Mark C. DNA bridging and looping by HMO1 provides a mechanism for stabilizing nucleosome-free chromatin. Nucleic Acids Research. 2014, 42 (14): 8996–9004. PMC 4132745 . PMID 25063301. doi:10.1093/nar/gku635.
^ Murugesapillai, Divakaran; McCauley, Micah J.; Maher, L. James; Williams, Mark C. Single-molecule studies of high-mobility group B architectural DNA bending proteins. Biophysical Reviews. 2017, 9 (1): 17–40. PMC 5331113 . PMID 28303166. doi:10.1007/s12551-016-0236-4.
^ Myers L, Kornberg R. Mediator of transcriptional regulation. Annu Rev Biochem. 2000, 69 (1): 729–49. PMID 10966474. doi:10.1146/annurev.biochem.69.1.729.
^ Li Z, Van Calcar S, Qu C, Cavenee W, Zhang M, Ren B. A global transcriptional regulatory role for c-Myc in Burkitt's lymphoma cells. Proc Natl Acad Sci USA. 2003, 100 (14): 8164–9. Bibcode:2003PNAS..100.8164L. PMC 166200 . PMID 12808131. doi:10.1073/pnas.1332764100 .

[1] Travers, A. A. DNA-protein interactions. London: Springer. 1993. ISBN 978-0-412-25990-6.

[2] Pabo CO, Sauer RT. Protein-DNA recognition. Annu. Rev. Biochem. 1984, 53 (1): 293–321. PMID 6236744. doi:10.1146/annurev.bi.53.070184.001453.

[3] Dickerson R.E. The DNA helix and how it is read. Sci Am. 1983, 249 (6): 94–111. Bibcode:1983SciAm.249f..94D. doi:10.1038/scientificamerican1283-94.

[4] Zimmer C, Wähnert U. Nonintercalating DNA-binding ligands: specificity of the interaction and their use as tools in biophysical, biochemical and biological investigations of the genetic material. Prog. Biophys. Mol. Biol. 1986, 47 (1): 31–112. PMID 2422697. doi:10.1016/0079-6107(86)90005-2 .

[5] Dervan PB. Design of sequence-specific DNA-binding molecules. Science. April 1986, 232 (4749): 464–71. Bibcode:1986Sci...232..464D. PMID 2421408. doi:10.1126/science.2421408.

[pmid9646864-6] Bewley CA, Gronenborn AM, Clore GM. Minor groove-binding architectural proteins: structure, function, and DNA recognition. Annu Rev Biophys Biomol Struct. 1998, 27: 105–31. PMC 4781445 . PMID 9646864. doi:10.1146/annurev.biophys.27.1.105.

[explore-7] Ganji, Mahipal; Docter, Margreet; Le Grice, Stuart F. J.; Abbondanzieri, Elio A. DNA binding proteins explore multiple local configurations during docking via rapid rebinding. Nucleic Acids Research. 2016-09-30, 44 (17): 8376–8384. ISSN 0305-1048. PMC 5041478 . PMID 27471033. doi:10.1093/nar/gkw666.

[pmid21929364-8] Clark KJ, Voytas DF, Ekker SC. A TALE of two nucleases: gene targeting for the masses?. Zebrafish. September 2011, 8 (3): 147–9. PMC 3174730 . PMID 21929364. doi:10.1089/zeb.2011.9993.

[pmid22842750-9] Cai YH, Huang H. Advances in the study of protein–DNA interaction. Amino Acids. July 2012, 43 (3): 1141–6. PMID 22842750. S2CID 310256. doi:10.1007/s00726-012-1377-9.

[10] Fried M, Crothers DM. Equilibria and kinetics of lac repressor-operator interactions by polyacrylamide gel electrophoresis. Nucleic Acids Res. 1981, 9 (23): 6505–6525. PMC 327619 . PMID 6275366. doi:10.1093/nar/9.23.6505.

[11] Garner MM, Revzin A. A gel electrophoresis method for quantifying the binding of proteins to specific DNA regions: application to components of the Escherichia coli lactose operon regulatory system. Nucleic Acids Res. 1981, 9 (13): 3047–3060. PMC 327330 . PMID 6269071. doi:10.1093/nar/9.13.3047.

[12] Brand LH, Kirchler T, Hummel S, Chaban C, Wanke D. DPI-ELISA: a fast and versatile method to specify the binding of plant transcription factors to DNA in vitro.. Plant Methods. 2010, 25 (6): 25. PMC 3003642 . PMID 21108821. doi:10.1186/1746-4811-6-25 .

[13] Galas DJ, Schmitz A. DNAse footprinting: a simple method for the detection of protein-DNA binding specificity. Nucleic Acids Res. 1978, 5 (9): 3157–3170. PMC 342238 . PMID 212715. doi:10.1093/nar/5.9.3157.

[pmid20077036-14] Collas, Philippe. The Current State of Chromatin Immunoprecipitation. Molecular Biotechnology. January 2010, 45 (1): 87–100. PMID 20077036. doi:10.1007/s12033-009-9239-8.

[15] Luger K, Mäder A, Richmond R, Sargent D, Richmond T. Crystal structure of the nucleosome core particle at 2.8 A resolution. Nature. 1997, 389 (6648): 251–60. Bibcode:1997Natur.389..251L. PMID 9305837. S2CID 4328827. doi:10.1038/38444.

[16] Jenuwein T, Allis C. Translating the histone code. Science. 2001, 293 (5532): 1074–80. CiteSeerX 10.1.1.453.900 . PMID 11498575. S2CID 1883924. doi:10.1126/science.1063127.

[17] Thomas J. HMG1 and 2: architectural DNA-binding proteins. Biochem Soc Trans. 2001, 29 (Pt 4): 395–401. PMID 11497996. doi:10.1042/BST0290395.

[18] Murugesapillai, Divakaran; McCauley, Micah J.; Huo, Ran; Nelson Holte, Molly H.; Stepanyants, Armen; Maher, L. James; Israeloff, Nathan E.; Williams, Mark C. DNA bridging and looping by HMO1 provides a mechanism for stabilizing nucleosome-free chromatin. Nucleic Acids Research. 2014, 42 (14): 8996–9004. PMC 4132745 . PMID 25063301. doi:10.1093/nar/gku635.

[19] Murugesapillai, Divakaran; McCauley, Micah J.; Maher, L. James; Williams, Mark C. Single-molecule studies of high-mobility group B architectural DNA bending proteins. Biophysical Reviews. 2017, 9 (1): 17–40. PMC 5331113 . PMID 28303166. doi:10.1007/s12551-016-0236-4.

[20] Myers L, Kornberg R. Mediator of transcriptional regulation. Annu Rev Biochem. 2000, 69 (1): 729–49. PMID 10966474. doi:10.1146/annurev.biochem.69.1.729.

[21] Li Z, Van Calcar S, Qu C, Cavenee W, Zhang M, Ren B. A global transcriptional regulatory role for c-Myc in Burkitt's lymphoma cells. Proc Natl Acad Sci USA. 2003, 100 (14): 8164–9. Bibcode:2003PNAS..100.8164L. PMC 166200 . PMID 12808131. doi:10.1073/pnas.1332764100 .

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