DEAD box
DEAD box为一蛋白质家族的通称，在原核生物与真核生物细胞中皆有，因其中一个结构域有一天门冬胺酸-麸胺酸-丙胺酸-天门冬胺酸（DEAD）的氨基酸序列而得名[2]。此家族的蛋白多参与RNA相关反应[3]，有许多蛋白为RNA解旋酶[4]，可以消耗ATP的机制将双股RNA解开[5]。
| DEAD/DEAH box RNA解旋酶 | |||||||||
|---|---|---|---|---|---|---|---|---|---|
 | |||||||||
| 鉴定 | |||||||||
| 标志 | DEAD | ||||||||
| Pfam | PF00270（旧版） | ||||||||
| Pfam宗系 | CL0023（旧版） | ||||||||
| InterPro | IPR011545 | ||||||||
| PROSITE | PDOC00039 | ||||||||
| SCOP | 1qva / SUPFAM | ||||||||
| CDD | cd00268 | ||||||||
| |||||||||
DEAH家族与SKI2家族的蛋白序列也与DEAD box家族的蛋白相似[6][7][8]，三者合称DExD/H家族蛋白[9]。
结构
1980年代晚期有学者发现许多蛋白的NTP结合位点序列和eIF4ARNA解旋酶的相似[10]，后续研究发现这些蛋白均有9个保守的结构域，由N端至C端分别为Q结构域、结构域I、结构域Ia、结构域Ib、结构域II、结构域III、结构域IV、结构域V与结构域VI，其中结构域II又名沃克结构域-B，包含天门冬胺酸-麸胺酸-丙胺酸-天门冬胺酸（DEAD）的氨基酸序列[2]。Q结构域、结构域I、结构域II与结构域VI为结合与水解ATP所需，结构域Ia、结构域Ib、结构域III、结构域IV与结构域V则为结合RNA所需[11]。
功能
DEAD box家族的蛋白多为RNA解旋酶，参与转录、RNA剪接、核糖体组装、RNA转运、转译与RNA降解等细胞中的多种RNA相关反应[9][12][13]。
酿酒酵母mRNA剪接的过程有Sub2、Prp28与Prp5等3种DEAD box蛋白参与[5]，其中Prp5可与U2 SnRNA结合以影响其结构，使其得以与mRNA内含子中的分支位点（branchpoint）结合[14]；Prp28可能可识别内含子的5′端切割位点，但此蛋白无解旋酶活性[15]。另外Prp2、Prp16、Prp22、Prp43与Brr213等多种DEAH家族蛋白也参与mRNA剪切[16]。
转译起始因子eIF4A为一DEAD box蛋白，在转译起始时可解开mRNA5′ UTR的二级结构，以利核糖体小次单元扫描mRNA以寻找起始密码子[17]。另一DEAD box Ded1也参与转译起始过程，但具体机制仍不明[18]；还有一与Ded1相似的DEAD box蛋白Vasa可与eIF2互动[19]。
参考文献
- ^ Johnson, E. R.; McKay, D. B. Crystallographic structure of the amino terminal domain of yeast initiation factor 4A, a representative DEAD-box RNA helicase. RNA. 1999, 5 (12): 1526–1534. PMC 1369875
. PMID 10606264. doi:10.1017/S1355838299991410.
- ^ 2.0 2.1 Linder, P.; Lasko, P. F.; Ashburner, M.; Leroy, P.; Nielsen, P. J.; Nishi, K.; Schnier, J.; Slonimski, P. P. Birth of the D-E-A-D box. Nature. 1989, 337 (6203): 121–122. Bibcode:1989Natur.337..121L. PMID 2563148. S2CID 13529955. doi:10.1038/337121a0.
- ^ Takashi Kikuma; Masaya Ohtsu; Takahiko Utsugi; Shoko Koga; Kohji Okuhara; Toshihiko Eki; Fumihiro Fujimori; Yasufumi Murakami. Dbp9p, a Member of the DEAD Box Protein Family, Exhibits DNA Helicase Activity. J. Biol. Chem. March 2004, 279 (20): 20692–20698. PMID 15028736. doi:10.1074/jbc.M400231200 .
- ^ Heung LJ, Del Poeta M. Unlocking the DEAD-box: a key to cryptococcal virulence?. J. Clin. Invest. March 2005, 115 (3): 593–5. PMC 1052016 . PMID 15765144. doi:10.1172/JCI24508.
- ^ 5.0 5.1 Linder P. Dead-box proteins: a family affair—active and passive players in RNP-remodeling. Nucleic Acids Res. 2006, 34 (15): 4168–80. PMC 1616962 . PMID 16936318. doi:10.1093/nar/gkl468.
- ^ Tanaka N, Schwer B. Characterization of the NTPase, RNA-binding, and RNA helicase activities of the DEAH-box splicing factor Prp22. Biochemistry. July 2005, 44 (28): 9795–803. PMID 16008364. doi:10.1021/bi050407m.
- ^ Xu J, Wu H, Zhang C, Cao Y, Wang L, Zeng L, Ye X, Wu Q, Dai J, Xie Y, Mao Y. Identification of a novel human DDX40gene, a new member of the DEAH-box protein family. J. Hum. Genet. 2002, 47 (12): 681–3. PMID 12522690. doi:10.1007/s100380200104 .
- ^ Wang L, Lewis MS, Johnson AW. Domain interactions within the Ski2/3/8 complex and between the Ski complex and Ski7p. RNA. August 2005, 11 (8): 1291–302. PMC 1370812 . PMID 16043509. doi:10.1261/rna.2060405.
- ^ 9.0 9.1 de la Cruz J, Kressler D, Linder P. Unwinding RNA in Saccharomyces cerevisiae: DEAD-box proteins and related families. Trends Biochem. Sci. May 1999, 24 (5): 192–8. PMID 10322435. doi:10.1016/S0968-0004(99)01376-6.
- ^ Gorbalenya AE, Koonin EV, Donchenko AP, Blinov VM. Two related superfamilies of putative helicases involved in replication, recombination, repair and expression of DNA and RNA genomes. Nucleic Acids Res. June 1989, 17 (12): 4713–30. PMC 318027 . PMID 2546125. doi:10.1093/nar/17.12.4713.
- ^ Tanner NK, Cordin O, Banroques J, Doère M, Linder P. The Q motif: a newly identified motif in DEAD box helicases may regulate ATP binding and hydrolysis. Mol. Cell. January 2003, 11 (1): 127–38. PMID 12535527. doi:10.1016/S1097-2765(03)00006-6 .
- ^ Aubourg S, Kreis M, Lecharny A. The DEAD box RNA helicase family in Arabidopsis thaliana. Nucleic Acids Res. January 1999, 27 (2): 628–36. PMC 148225 . PMID 9862990. doi:10.1093/nar/27.2.628.
- ^ Staley JP, Guthrie C. Mechanical devices of the spliceosome: motors, clocks, springs, and things. Cell. February 1998, 92 (3): 315–26. PMID 9476892. S2CID 6208113. doi:10.1016/S0092-8674(00)80925-3 .
- ^ Ghetti A, Company M, Abelson J. Specificity of Prp24 binding to RNA: a role for Prp24 in the dynamic interaction of U4 and U6 snRNAs. RNA. April 1995, 1 (2): 132–45. PMC 1369067 . PMID 7585243.
- ^ Strauss EJ, Guthrie C. PRP28, a 'DEAD-box' protein, is required for the first step of mRNA splicing in vitro. Nucleic Acids Res. August 1994, 22 (15): 3187–93. PMC 310295 . PMID 7520570. doi:10.1093/nar/22.15.3187.
- ^ Silverman E, Edwalds-Gilbert G, Lin RJ. DExD/H-box proteins and their partners: helping RNA helicases unwind. Gene. July 2003, 312: 1–16. PMID 12909336. doi:10.1016/S0378-1119(03)00626-7.
- ^ Sonenberg N. Cap-binding proteins of eukaryotic messenger RNA: functions in initiation and control of translation. Prog. Nucleic Acid Res. Mol. Biol. Progress in Nucleic Acid Research and Molecular Biology. 1988, 35: 173–207. ISBN 978-0-12-540035-0. PMID 3065823. doi:10.1016/S0079-6603(08)60614-5.
- ^ Berthelot K, Muldoon M, Rajkowitsch L, Hughes J, McCarthy JE. Dynamics and processivity of 40S ribosome scanning on mRNA in yeast. Mol. Microbiol. February 2004, 51 (4): 987–1001. PMID 14763975. doi:10.1046/j.1365-2958.2003.03898.x .
- ^ Carrera P, Johnstone O, Nakamura A, Casanova J, Jäckle H, Lasko P. VASA mediates translation through interaction with a Drosophila yIF2 homolog. Mol. Cell. January 2000, 5 (1): 181–7. PMID 10678180. doi:10.1016/S1097-2765(00)80414-1. hdl:11858/00-001M-0000-0012-F80E-6 .
