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DEAD box

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DEAD/DEAH box helicase
Structure of the amino terminal domain of yeast initiation factor 4A. PDB1qva[1]
Identifiers
SymbolDEAD
PfamPF00270
PfamclanCL0023
InterProIPR011545
PROSITEPDOC00039
SCOP21qva/SCOPe/SUPFAM
CDDcd00268
Available protein structures:
Pfam structures/ECOD
PDBRCSB PDB;PDBe;PDBj
PDBsumstructure summary

DEAD box proteinsare involved in an assortment of metabolic processes that typically involveRNAs,but in some cases also othernucleic acids.[2]They are highly conserved in ninemotifsand can be found in mostprokaryotesandeukaryotes,but not all. Many organisms, including humans, contain DEAD-box (SF2)helicases,which are involved in RNAmetabolism.[3]

DEAD box family

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DEAD box proteins were first brought to attention in the late 1980s in a study that looked at a group ofNTP binding sitesthat 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 motif from the N-terminal to the C-terminal are named 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 theWalker B motifand 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]

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The DEAH andSKI2families 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[which?]that are conserved within their own family.[10]

DEAD box, DEAH, and the SKI2 families are collectively referred to asDExD/H proteins.[10]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

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DEAD box proteins are considered to be RNA helicases and many have been found to be required in cellular processes such asRNAmetabolism, including nucleartranscription,pre-mRNA splicing,ribosomebiogenesis,nucleocytoplasmic transport, translation, RNA decay and organellar gene expression.[10][11][12]

Pre-mRNA splicing

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Main article:RNA 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.[13]There are three DEAD box proteins in the yeast system, Sub2, Prp28, and Prp5, which have been proven to be required for in vivo splicing.[13]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.[14]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.[15]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.[16]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 thetransesterifications,release of the mRNA, and recycling of the spliceosome complex9.

The role of DEAD box proteins in pre-mRNA splicing. The orange text represents the DEAD box proteins.

Translation initiation

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Main article:Protein translation

TheeIF4Atranslation initiation factor was the first DEAD box protein found to have an RNA-dependentATPaseactivity. It has been proposed that this abundant protein helps in unwinding the secondary structure in the 5'-untranslated region.[17]This can inhibit the scanning process of the small ribosomal subunit, if not unwound.[17]Ded1is another DEAD box protein that is also needed for translation initiation, but its exact role in this process is still obscure.[18]Vasa,a DEAD box protein highly related to Ded1 plays a part in translation initiation by interacting with eukaryotic initiation factor 2 (eIF2).[19]

See also

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References

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  1. ^Johnson, E. R.; McKay, D. B. (1999)."Crystallographic structure of the amino terminal domain of yeast initiation factor 4A, a representative DEAD-box RNA helicase".RNA.5(12): 1526–1534.doi:10.1017/S1355838299991410.PMC1369875.PMID10606264.
  2. ^Takashi Kikuma; Masaya Ohtsu; Takahiko Utsugi; Shoko Koga; Kohji Okuhara; Toshihiko Eki; Fumihiro Fujimori; Yasufumi Murakami (March 2004)."Dbp9p, a Member of the DEAD Box Protein Family, Exhibits DNA Helicase Activity".J. Biol. Chem.279(20): 20692–20698.doi:10.1074/jbc.M400231200.PMID15028736.
  3. ^Heung LJ,Del Poeta M(March 2005)."Unlocking the DEAD-box: a key to cryptococcal virulence?".J. Clin. Invest.115(3): 593–5.doi:10.1172/JCI24508.PMC1052016.PMID15765144.
  4. ^Gorbalenya AE, Koonin EV, Donchenko AP, Blinov VM (June 1989)."Two related superfamilies of putative helicases involved in replication, recombination, repair and expression of DNA and RNA genomes".Nucleic Acids Res.17(12): 4713–30.doi:10.1093/nar/17.12.4713.PMC318027.PMID2546125.
  5. ^abcLinder, P.; Lasko, P. F.; Ashburner, M.; Leroy, P.; Nielsen, P. J.; Nishi, K.; Schnier, J.; Slonimski, P. P. (1989). "Birth of the D-E-A-D box".Nature.337(6203): 121–122.Bibcode:1989Natur.337..121L.doi:10.1038/337121a0.PMID2563148.S2CID13529955.
  6. ^abTanner NK, Cordin O, Banroques J, Doère M, Linder P (January 2003)."The Q motif: a newly identified motif in DEAD box helicases may regulate ATP binding and hydrolysis".Mol. Cell.11(1): 127–38.doi:10.1016/S1097-2765(03)00006-6.PMID12535527.
  7. ^Tanaka N, Schwer B (July 2005). "Characterization of the NTPase, RNA-binding, and RNA helicase activities of the DEAH-box splicing factor Prp22".Biochemistry.44(28): 9795–803.doi:10.1021/bi050407m.PMID16008364.
  8. ^Xu J, Wu H, Zhang C, Cao Y, Wang L, Zeng L, Ye X, Wu Q, Dai J, Xie Y, Mao Y (2002)."Identification of a novel human DDX40gene, a new member of the DEAH-box protein family".J. Hum. Genet.47(12): 681–3.doi:10.1007/s100380200104.PMID12522690.
  9. ^Wang L, Lewis MS, Johnson AW (August 2005)."Domain interactions within the Ski2/3/8 complex and between the Ski complex and Ski7p".RNA.11(8): 1291–302.doi:10.1261/rna.2060405.PMC1370812.PMID16043509.
  10. ^abcde la Cruz J, Kressler D, Linder P (May 1999). "Unwinding RNA in Saccharomyces cerevisiae: DEAD-box proteins and related families".Trends Biochem. Sci.24(5): 192–8.doi:10.1016/S0968-0004(99)01376-6.PMID10322435.
  11. ^Aubourg S, Kreis M, Lecharny A (January 1999)."The DEAD box RNA helicase family in Arabidopsis thaliana".Nucleic Acids Res.27(2): 628–36.doi:10.1093/nar/27.2.628.PMC148225.PMID9862990.
  12. ^Staley JP, Guthrie C (February 1998)."Mechanical devices of the spliceosome: motors, clocks, springs, and things".Cell.92(3): 315–26.doi:10.1016/S0092-8674(00)80925-3.PMID9476892.S2CID6208113.
  13. ^abLinder P (2006)."Dead-box proteins: a family affair—active and passive players in RNP-remodeling".Nucleic Acids Res.34(15): 4168–80.doi:10.1093/nar/gkl468.PMC1616962.PMID16936318.
  14. ^Ghetti A, Company M, Abelson J (April 1995)."Specificity of Prp24 binding to RNA: a role for Prp24 in the dynamic interaction of U4 and U6 snRNAs".RNA.1(2): 132–45.PMC1369067.PMID7585243.
  15. ^Strauss EJ, Guthrie C (August 1994)."PRP28, a 'DEAD-box' protein, is required for the first step of mRNA splicing in vitro".Nucleic Acids Res.22(15): 3187–93.doi:10.1093/nar/22.15.3187.PMC310295.PMID7520570.
  16. ^Silverman E, Edwalds-Gilbert G, Lin RJ (July 2003). "DExD/H-box proteins and their partners: helping RNA helicases unwind".Gene.312:1–16.doi:10.1016/S0378-1119(03)00626-7.PMID12909336.
  17. ^abSonenberg N (1988).Cap-binding proteins of eukaryotic messenger RNA: functions in initiation and control of translation.Progress in Nucleic Acid Research and Molecular Biology. Vol. 35. pp. 173–207.doi:10.1016/S0079-6603(08)60614-5.ISBN978-0-12-540035-0.PMID3065823.
  18. ^Berthelot K, Muldoon M, Rajkowitsch L, Hughes J, McCarthy JE (February 2004)."Dynamics and processivity of 40S ribosome scanning on mRNA in yeast".Mol. Microbiol.51(4): 987–1001.doi:10.1046/j.1365-2958.2003.03898.x.PMID14763975.
  19. ^Carrera P, Johnstone O, Nakamura A, Casanova J, Jäckle H, Lasko P (January 2000). "VASA mediates translation through interaction with a Drosophila yIF2 homolog".Mol. Cell.5(1): 181–7.doi:10.1016/S1097-2765(00)80414-1.hdl:11858/00-001M-0000-0012-F80E-6.PMID10678180.
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