DEAD box

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.{{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}} 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. There were nine common sequences found to be conserved amongst the studied species, which is an important criterion of the DEAD box family.{{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

|bibcode = 1989Natur.337..121L | s2cid = 13529955

}}

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 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”. 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.{{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| doi-access = free }}

{{missing information|section|comparison of motif structure|small=yes|date=October 2021}}

The DEAH and SKI2 families have had proteins that have been identified to be related to the DEAD box family.{{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 }}{{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 | doi-access = free }}{{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 }} These two relatives have a few particularly unique motifs{{which|date=October 2021}} that are conserved within their own family.

DEAD box, DEAH, and the SKI2 families are collectively referred to as DExD/H proteins.{{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}} 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.

DEAD box proteins are considered to be RNA helicases and many have been found to be required in cellular processes such as RNA metabolism, including nuclear transcription, pre-mRNA splicing, ribosome biogenesis, nucleocytoplasmic transport, translation, RNA decay and organellar gene expression.{{cite journal | vauthors = Aubourg S, Kreis M, Lecharny A | title = The DEAD box RNA helicase family in Arabidopsis thaliana | journal = Nucleic Acids Res. | volume = 27 | issue = 2 | pages = 628–36 |date=January 1999 | pmid = 9862990 | pmc = 148225 | doi = 10.1093/nar/27.2.628| url = }}{{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| s2cid = 6208113 | doi-access = free }}

{{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.{{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 }} 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. 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.{{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 }} 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.{{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}} 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.{{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 | pages = 1–16 |date=July 2003 | pmid = 12909336 | doi = 10.1016/S0378-1119(03)00626-7}} 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.

File:Spliceosome405.jpg

{{main article|Protein translation}}

The eIF4A translation initiation factor was the first DEAD box protein found to have an RNA-dependent ATPase activity. It has been proposed that this abundant protein helps in unwinding the secondary structure in the 5'-untranslated region. This can inhibit the scanning process of the small ribosomal subunit, if not unwound.{{cite book | author = Sonenberg N | title = Cap-binding proteins of eukaryotic messenger RNA: functions in initiation and control of translation| volume = 35 | pages = 173–207 | year = 1988 | pmid = 3065823 | doi = 10.1016/S0079-6603(08)60614-5| series = Progress in Nucleic Acid Research and Molecular Biology | isbn = 978-0-12-540035-0 }} Ded1 is another DEAD box protein that is also needed for translation initiation, but its exact role in this process is still obscure.{{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| doi-access = free }} Vasa, a DEAD box protein highly related to Ded1 plays a part in translation initiation by interacting with eukaryotic initiation factor 2 (eIF2).{{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| hdl = 11858/00-001M-0000-0012-F80E-6 | hdl-access = free }}

• DDX3X
• DEAD/DEAH box helicase
• RNA helicase
• Walker A motif

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Category:Protein domains