“DEAD box”的意思、由来-开放百科全书

DEAD box proteins were first brought to attention in the late 1980s in a study that looked at a group of NTP binding sites that were similar in sequence to the eIF4A RNA helicase sequence.^[4] The results of this study showed that these proteins (p68, SrmB, MSS116, vasa, PL10, mammalian eIF4A, yeast eIF4A) involved in RNA metabolism had several common elements.^[5] There were nine common sequences found to be conserved amongst the studied species, which is an important criterion of the DEAD box family.^[5] The nine conserved motifs are as follows, Q-motif, motif 1, motif 1a, motif 1b, motif II, motif III, motif IV, motif V, and motif VI, as shown in the figure. Motif II is also known as the Walker B motif and contains the amino acid sequence D-E-A-D (asp-glu-ala-asp), which gave this family of proteins the name “DEAD box”.^[5] Motif 1, motif II, the Q motif, and motif VI are all needed for ATP binding and hydrolysis, while motifs, 1a, 1b, III, IV, and V may be involved in intramolecular rearrangements and RNA interaction.^[6]

Related families

The DEAH and SKI families have had proteins that have been identified to be related to the DEAD box family.^[7]^[8]^[9] These two relatives have a few particularly unique motifs that are conserved within their own family. DEAD box, DEAH, and the SKI families are all referred to as DExD/H proteins.^[10] They are all quite distinct from one another and there is not one protein that belongs to more than one of these families. It is thought that each family has a specific role in RNA metabolism, for example both DEAD box and DEAH box proteins NTPase activities become stimulated by RNA, but DEAD box proteins use ATP and DEAH does not.^[6]

Biological functions

DEAD box proteins are considered to be RNA helicases and many have been found to be required in cellular processes such as pre-mRNA processing and rearranging of ribonucleoproteins (RNP) complexes.^[11]

Pre-mRNA splicing

Pre-mRNA splicing requires rearrangements of five large RNP complexes, which are snRNPs U1, U2, U4, U5, and U6. DEAD box proteins are helicases that perform unwinding in an energy dependent approach and are able to perform these snRNP rearrangements in a quick and efficient manner.^[12] There are three DEAD box proteins in the yeast system, Sub2, Prp28, and Prp5, and have been proven to be required for in vivo splicing.^[12] Prp5 has been shown to assist in a conformational rearrangement of U2 snRNA, which makes the branch point recognition sequence of U2 available to bind the branch point sequence.^[13] Prp28 may have a role in recognizing the 5’ splice site and does not display RNA helicase activity, suggesting that other factors must be present in order to activate Prp28.^[14] DExD/H proteins have also been found to be required components in pre- mRNA splicing, in particular the DEAH proteins, Prp2, Prp16, Prp22, Prp43, and Brr213.^[15] As shown in the figure, DEAD box proteins are needed in the initial steps of spliceosome formation, while DEAH box proteins are indirectly required for the transesterifications, release of the mRNA, and recycling of the spliceosome complex9.

Translation initiation

The eIF4A translation initiation factor was the first DEAD box protein found to have a RNA dependent ATPase activity. It has been proposed that this abundant protein helps in unwinding the secondary structure in the 5'-untranslated region.^[20] This can inhibit the scanning process of the small ribosomal subunit, if not unwound.^[16] Ded1 is another DEAD box protein that is also needed for translation initiation, but its exact role in this process is still obscure.^[17] Vasa, a DEAD box protein highly related to Ded1 plays a part in translation initiation by interacting with eukaryotic initiation factor 2 (eIF2).^[18]

See also

References

1. ^{{Cite journal | last1 = Johnson | first1 = E. R. | last2 = McKay | first2 = D. B. | title = Crystallographic structure of the amino terminal domain of yeast initiation factor 4A, a representative DEAD-box RNA helicase | journal = RNA | volume = 5 | issue = 12 | pages = 1526–1534 | year = 1999 | pmid = 10606264 | pmc = 1369875 | doi=10.1017/S1355838299991410}}
2. ^{{cite journal |author1=Takashi Kikuma |author2=Masaya Ohtsu |author3=Takahiko Utsugi |author4=Shoko Koga |author5=Kohji Okuhara |author6=Toshihiko Eki |author7=Fumihiro Fujimori |author8=Yasufumi Murakami | title = Dbp9p, a Member of the DEAD Box Protein Family, Exhibits DNA Helicase Activity | journal = J. Biol. Chem. | volume = 279 | issue = 20 | pages = 20692–20698 |date=March 2004 | pmid = 15028736 | pmc = | doi = 10.1074/jbc.M400231200 | url = }}
3. ^{{cite journal |vauthors=Heung LJ, Del Poeta M | title = Unlocking the DEAD-box: a key to cryptococcal virulence? | journal = J. Clin. Invest. | volume = 115 | issue = 3 | pages = 593–5 |date=March 2005 | pmid = 15765144 | pmc = 1052016 | doi = 10.1172/JCI24508 | url = }}
4. ^{{cite journal |vauthors=Gorbalenya AE, Koonin EV, Donchenko AP, Blinov VM | title = Two related superfamilies of putative helicases involved in replication, recombination, repair and expression of DNA and RNA genomes | journal = Nucleic Acids Res. | volume = 17 | issue = 12 | pages = 4713–30 |date=June 1989 | pmid = 2546125 | pmc = 318027 | doi = 10.1093/nar/17.12.4713| url = }}
5. ^¹²{{Cite journal | last1 = Linder | first1 = P. | last2 = Lasko | first2 = P. F. | last3 = Ashburner | first3 = M. | last4 = Leroy | first4 = P. | last5 = Nielsen | first5 = P. J. | last6 = Nishi | first6 = K. | last7 = Schnier | first7 = J. | last8 = Slonimski | first8 = P. P. | doi = 10.1038/337121a0 | title = Birth of the D-E-A-D box | journal = Nature | volume = 337 | issue = 6203 | pages = 121–122 | year = 1989 | pmid = 2563148 | pmc = |bibcode = 1989Natur.337..121L }}
6. ^¹{{cite journal |vauthors=Tanner NK, Cordin O, Banroques J, Doère M, Linder P | title = The Q motif: a newly identified motif in DEAD box helicases may regulate ATP binding and hydrolysis | journal = Mol. Cell | volume = 11 | issue = 1 | pages = 127–38 |date=January 2003 | pmid = 12535527 | doi = 10.1016/S1097-2765(03)00006-6| url = }}
7. ^{{cite journal |vauthors=Tanaka N, Schwer B | title = Characterization of the NTPase, RNA-binding, and RNA helicase activities of the DEAH-box splicing factor Prp22 | journal = Biochemistry | volume = 44 | issue = 28 | pages = 9795–803 |date=July 2005 | pmid = 16008364 | doi = 10.1021/bi050407m | url = }}
8. ^{{cite journal |vauthors=Xu J, Wu H, Zhang C, Cao Y, Wang L, Zeng L, Ye X, Wu Q, Dai J, Xie Y, Mao Y | title = Identification of a novel human DDX40gene, a new member of the DEAH-box protein family | journal = J. Hum. Genet. | volume = 47 | issue = 12 | pages = 681–3 | year = 2002 | pmid = 12522690 | doi = 10.1007/s100380200104 | url = }}
9. ^{{cite journal |vauthors=Wang L, Lewis MS, Johnson AW | title = Domain interactions within the Ski2/3/8 complex and between the Ski complex and Ski7p | journal = RNA | volume = 11 | issue = 8 | pages = 1291–302 |date=August 2005 | pmid = 16043509 | pmc = 1370812 | doi = 10.1261/rna.2060405 | url = }}
10. ^{{cite journal |vauthors=de la Cruz J, Kressler D, Linder P | title = Unwinding RNA in Saccharomyces cerevisiae: DEAD-box proteins and related families | journal = Trends Biochem. Sci. | volume = 24 | issue = 5 | pages = 192–8 |date=May 1999 | pmid = 10322435 | doi = 10.1016/S0968-0004(99)01376-6| url = }}
11. ^{{cite journal |vauthors=Staley JP, Guthrie C | title = Mechanical devices of the spliceosome: motors, clocks, springs, and things | journal = Cell | volume = 92 | issue = 3 | pages = 315–26 |date=February 1998 | pmid = 9476892 | doi = 10.1016/S0092-8674(00)80925-3| url = }}
12. ^¹{{cite journal | author = Linder P | title = Dead-box proteins: a family affair—active and passive players in RNP-remodeling | journal = Nucleic Acids Res. | volume = 34 | issue = 15 | pages = 4168–80 | year = 2006 | pmid = 16936318 | pmc = 1616962 | doi = 10.1093/nar/gkl468 | url = }}
13. ^{{cite journal |vauthors=Ghetti A, Company M, Abelson J | title = Specificity of Prp24 binding to RNA: a role for Prp24 in the dynamic interaction of U4 and U6 snRNAs | journal = RNA | volume = 1 | issue = 2 | pages = 132–45 |date=April 1995 | pmid = 7585243 | pmc = 1369067 | doi = | url = }}
14. ^{{cite journal |vauthors=Strauss EJ, Guthrie C | title = PRP28, a 'DEAD-box' protein, is required for the first step of mRNA splicing in vitro | journal = Nucleic Acids Res. | volume = 22 | issue = 15 | pages = 3187–93 |date=August 1994 | pmid = 7520570 | pmc = 310295 | doi = 10.1093/nar/22.15.3187| url = }}
15. ^{{cite journal |vauthors=Silverman E, Edwalds-Gilbert G, Lin RJ | title = DExD/H-box proteins and their partners: helping RNA helicases unwind | journal = Gene | volume = 312 | issue = | pages = 1–16 |date=July 2003 | pmid = 12909336 | doi = 10.1016/S0378-1119(03)00626-7| url = }}
16. ^¹{{cite book | author = Sonenberg N | title = Cap-binding proteins of eukaryotic messenger RNA: functions in initiation and control of translation | journal = Prog. Nucleic Acid Res. Mol. Biol. | volume = 35 | issue = | pages = 173–207 | year = 1988 | pmid = 3065823 | doi = 10.1016/S0079-6603(08)60614-5| url = | series = Progress in Nucleic Acid Research and Molecular Biology | isbn = 978-0-12-540035-0 }}
17. ^{{cite journal |vauthors=Berthelot K, Muldoon M, Rajkowitsch L, Hughes J, McCarthy JE | title = Dynamics and processivity of 40S ribosome scanning on mRNA in yeast | journal = Mol. Microbiol. | volume = 51 | issue = 4 | pages = 987–1001 |date=February 2004 | pmid = 14763975 | doi = 10.1046/j.1365-2958.2003.03898.x| url = }}
18. ^{{cite journal |vauthors=Carrera P, Johnstone O, Nakamura A, Casanova J, Jäckle H, Lasko P | title = VASA mediates translation through interaction with a Drosophila yIF2 homolog | journal = Mol. Cell | volume = 5 | issue = 1 | pages = 181–7 |date=January 2000 | pmid = 10678180 | doi = 10.1016/S1097-2765(00)80414-1| url = }}