维基百科

DEAD box

DEAD box為一蛋白質家族的通稱，在原核生物與真核生物細胞中皆有，因其中一個結構域有一天門冬胺酸-麩胺酸-丙胺酸-天門冬胺酸（DEAD）的氨基酸序列而得名[2]。此家族的蛋白多參與RNA相關反應[3]，有許多蛋白為RNA解旋酶[4]，可以消耗ATP的機制將雙股RNA解開[5]。

DEAD/DEAH box RNA解旋酶
釀酒酵母的eIF4A結構（1qva）[1]
鑑定
標誌DEAD
PfamPF00270（旧版）
Pfam宗系CL0023（旧版）
InterPro（英语：InterPro）IPR011545
PROSITE（英语：PROSITE）PDOC00039
SCOP（英语：Structural Classification of Proteins）1qva / SUPFAM
CDD（英语：Conserved Domain Database）cd00268

DEAH家族與SKI2家族的蛋白序列也與DEAD box家族的蛋白相似[6][7][8]，三者合稱DExD/H家族蛋白[9]。

結構

编辑

1980年代晚期有學者發現許多蛋白的NTP結合位點（英语：NTP binding site）序列和eIF4ARNA解旋酶的相似[10]，後續研究發現這些蛋白均有9個保守的結構域，由N端至C端分別為Q結構域、結構域I、結構域Ia、結構域Ib、結構域II、結構域III、結構域IV、結構域V與結構域VI，其中結構域II又名沃克結構域-B（英语：Walker motifs），包含天門冬胺酸-麩胺酸-丙胺酸-天門冬胺酸（DEAD）的氨基酸序列[2]。Q結構域、結構域I、結構域II與結構域VI為結合與水解ATP所需，結構域Ia、結構域Ib、結構域III、結構域IV與結構域V則為結合RNA所需[11]。

功能

编辑
 
mRNA剪接過程，其中標註為橘色的蛋白皆屬DEAD box家族

DEAD box家族的蛋白多為RNA解旋酶，參與轉錄、RNA剪接、核糖體組裝（英语：ribosome biogenesis）、RNA轉運、轉譯與RNA降解等細胞中的多種RNA相關反應[9][12][13]。

釀酒酵母mRNA剪接的過程有Sub2、Prp28與Prp5等3種DEAD box蛋白參與[5]，其中Prp5可與U2 SnRNA（英语：U2 spliceosomal RNA）結合以影響其結構，使其得以與mRNA內含子中的分支位點（branchpoint）結合[14]；Prp28可能可識別內含子的5′端切割位點，但此蛋白無解旋酶活性[15]。另外Prp2、Prp16、Prp22、Prp43與Brr213等多種DEAH家族蛋白也參與mRNA剪切[16]。

轉譯起始因子eIF4A為一DEAD box蛋白，在轉譯起始時可解開mRNA5′ UTR的二級結構，以利核糖體小次單元掃描mRNA以尋找起始密碼子[17]。另一DEAD box Ded1也參與轉譯起始過程，但具體機制仍不明[18]；還有一與Ded1相似的DEAD box蛋白Vasa可與eIF2互動[19]。

參考文獻

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  1. ^ 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. ^ 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. 
  3. ^ 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  . 
  4. ^ 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. ^ 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. 
  6. ^ 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. 
  7. ^ 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  . 
  8. ^ 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. ^ 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. 
  10. ^ 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. 
  11. ^ 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  . 
  12. ^ 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. 
  13. ^ 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  . 
  14. ^ 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. 
  15. ^ 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. 
  16. ^ 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. 
  17. ^ 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. 
  18. ^ 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  . 
  19. ^ 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  . 
检索自“https://zh.wikipedia.org/w/index.php?title=DEAD_box&oldid=74140248”