5oo6

From Proteopedia

(Difference between revisions)

Current revision

Complex of human nuclear cap-binding complex with ARS2 C-terminal peptide

Structural highlights

5oo6 is a 24 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.8Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

NCBP1_HUMAN Component of the cap-binding complex (CBC), which binds cotranscriptionally to the 5'-cap of pre-mRNAs and is involved in various processes such as pre-mRNA splicing, translation regulation, nonsense-mediated mRNA decay, RNA-mediated gene silencing (RNAi) by microRNAs (miRNAs) and mRNA export. The CBC complex is involved in mRNA export from the nucleus via its interaction with ALYREF/THOC4/ALY, leading to the recruitment of the mRNA export machinery to the 5'-end of mRNA and to mRNA export in a 5' to 3' direction through the nuclear pore. The CBC complex is also involved in mediating U snRNA and intronless mRNAs export from the nucleus. The CBC complex is essential for a pioneer round of mRNA translation, before steady state translation when the CBC complex is replaced by cytoplasmic cap-binding protein eIF4E. The pioneer round of mRNA translation mediated by the CBC complex plays a central role in nonsense-mediated mRNA decay (NMD), NMD only taking place in mRNAs bound to the CBC complex, but not on eIF4E-bound mRNAs. The CBC complex enhances NMD in mRNAs containing at least one exon-junction complex (EJC) via its interaction with UPF1, promoting the interaction between UPF1 and UPF2. The CBC complex is also involved in 'failsafe' NMD, which is independent of the EJC complex, while it does not participate in Staufen-mediated mRNA decay (SMD). During cell proliferation, the CBC complex is also involved in microRNAs (miRNAs) biogenesis via its interaction with SRRT/ARS2 and is required for miRNA-mediated RNA interference. The CBC complex also acts as a negative regulator of PARN, thereby acting as an inhibitor of mRNA deadenylation. In the CBC complex, NCBP1/CBP80 does not bind directly capped RNAs (m7GpppG-capped RNA) but is required to stabilize the movement of the N-terminal loop of NCBP2/CBP20 and lock the CBC into a high affinity cap-binding state with the cap structure.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8] ^[9] ^[10] ^[11] ^[12]

Publication Abstract from PubMed

Pol II transcribes diverse classes of RNAs that need to be directed into the appropriate nuclear maturation pathway. All nascent Pol II transcripts are 5'-capped and the cap is immediately sequestered by the nuclear cap-binding complex (CBC). Mutually exclusive interactions of CBC with different partner proteins have been implicated in transcript fate determination. Here, we characterise the direct interactions between CBC and NELF-E, a subunit of the negative elongation factor complex, ARS2 and PHAX. Our biochemical and crystal structure results show that the homologous C-terminal peptides of NELF-E and ARS2 bind identically to CBC and in each case the affinity is enhanced when CBC is bound to a cap analogue. Furthermore, whereas PHAX forms a complex with CBC and ARS2, NELF-E binding to CBC is incompatible with PHAX binding. We thus define two mutually exclusive complexes CBC-NELF-E and CBC-ARS2-PHAX, which likely act in respectively earlier and later phases of transcription.

Structural basis for mutually exclusive co-transcriptional nuclear cap-binding complexes with either NELF-E or ARS2.,Schulze WM, Cusack S Nat Commun. 2017 Nov 3;8(1):1302. doi: 10.1038/s41467-017-01402-w. PMID:29101316^[13]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Izaurralde E, Lewis J, McGuigan C, Jankowska M, Darzynkiewicz E, Mattaj IW. A nuclear cap binding protein complex involved in pre-mRNA splicing. Cell. 1994 Aug 26;78(4):657-68. PMID:8069914
↑ Izaurralde E, Lewis J, Gamberi C, Jarmolowski A, McGuigan C, Mattaj IW. A cap-binding protein complex mediating U snRNA export. Nature. 1995 Aug 24;376(6542):709-12. PMID:7651522 doi:http://dx.doi.org/10.1038/376709a0
↑ Ishigaki Y, Li X, Serin G, Maquat LE. Evidence for a pioneer round of mRNA translation: mRNAs subject to nonsense-mediated decay in mammalian cells are bound by CBP80 and CBP20. Cell. 2001 Sep 7;106(5):607-17. PMID:11551508
↑ Chiu SY, Lejeune F, Ranganathan AC, Maquat LE. The pioneer translation initiation complex is functionally distinct from but structurally overlaps with the steady-state translation initiation complex. Genes Dev. 2004 Apr 1;18(7):745-54. Epub 2004 Apr 1. PMID:15059963 doi:http://dx.doi.org/10.1101/gad.1170204
↑ Lejeune F, Ranganathan AC, Maquat LE. eIF4G is required for the pioneer round of translation in mammalian cells. Nat Struct Mol Biol. 2004 Oct;11(10):992-1000. Epub 2004 Sep 7. PMID:15361857 doi:http://dx.doi.org/10.1038/nsmb824
↑ Hosoda N, Kim YK, Lejeune F, Maquat LE. CBP80 promotes interaction of Upf1 with Upf2 during nonsense-mediated mRNA decay in mammalian cells. Nat Struct Mol Biol. 2005 Oct;12(10):893-901. Epub 2005 Sep 25. PMID:16186820 doi:http://dx.doi.org/10.1038/nsmb995
↑ Cheng H, Dufu K, Lee CS, Hsu JL, Dias A, Reed R. Human mRNA export machinery recruited to the 5' end of mRNA. Cell. 2006 Dec 29;127(7):1389-400. PMID:17190602 doi:http://dx.doi.org/10.1016/j.cell.2006.10.044
↑ Balatsos NA, Nilsson P, Mazza C, Cusack S, Virtanen A. Inhibition of mRNA deadenylation by the nuclear cap binding complex (CBC). J Biol Chem. 2006 Feb 17;281(7):4517-22. Epub 2005 Nov 28. PMID:16317009 doi:http://dx.doi.org/10.1074/jbc.M508590200
↑ Matsuda D, Hosoda N, Kim YK, Maquat LE. Failsafe nonsense-mediated mRNA decay does not detectably target eIF4E-bound mRNA. Nat Struct Mol Biol. 2007 Oct;14(10):974-9. Epub 2007 Sep 16. PMID:17873884 doi:http://dx.doi.org/10.1038/nsmb1297
↑ Woeller CF, Gaspari M, Isken O, Maquat LE. NMD resulting from encephalomyocarditis virus IRES-directed translation initiation seems to be restricted to CBP80/20-bound mRNA. EMBO Rep. 2008 May;9(5):446-51. doi: 10.1038/embor.2008.36. Epub 2008 Mar 28. PMID:18369367 doi:http://dx.doi.org/10.1038/embor.2008.36
↑ Gruber JJ, Zatechka DS, Sabin LR, Yong J, Lum JJ, Kong M, Zong WX, Zhang Z, Lau CK, Rawlings J, Cherry S, Ihle JN, Dreyfuss G, Thompson CB. Ars2 links the nuclear cap-binding complex to RNA interference and cell proliferation. Cell. 2009 Jul 23;138(2):328-39. doi: 10.1016/j.cell.2009.04.046. PMID:19632182 doi:http://dx.doi.org/10.1016/j.cell.2009.04.046
↑ Kim KM, Cho H, Choi K, Kim J, Kim BW, Ko YG, Jang SK, Kim YK. A new MIF4G domain-containing protein, CTIF, directs nuclear cap-binding protein CBP80/20-dependent translation. Genes Dev. 2009 Sep 1;23(17):2033-45. doi: 10.1101/gad.1823409. Epub 2009 Jul 31. PMID:19648179 doi:http://dx.doi.org/10.1101/gad.1823409
↑ Schulze WM, Cusack S. Structural basis for mutually exclusive co-transcriptional nuclear cap-binding complexes with either NELF-E or ARS2. Nat Commun. 2017 Nov 3;8(1):1302. doi: 10.1038/s41467-017-01402-w. PMID:29101316 doi:http://dx.doi.org/10.1038/s41467-017-01402-w

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5oo6"

Categories: Homo sapiens | Large Structures | Cusack S | Schulze WM

@@ Line 3: / Line 3: @@
 <StructureSection load='5oo6' size='340' side='right'caption='[[5oo6]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5oo6]] is a 24 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5OO6 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5OO6 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5oo6]] is a 24 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5OO6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5OO6 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MGT:7N-METHYL-8-HYDROGUANOSINE-5-TRIPHOSPHATE'>MGT</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.8&#8491;</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5oo6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5oo6 OCA], [http://pdbe.org/5oo6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5oo6 RCSB], [http://www.ebi.ac.uk/pdbsum/5oo6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5oo6 ProSAT]</span></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MGT:7N-METHYL-8-HYDROGUANOSINE-5-TRIPHOSPHATE'>MGT</scene></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5oo6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5oo6 OCA], [https://pdbe.org/5oo6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5oo6 RCSB], [https://www.ebi.ac.uk/pdbsum/5oo6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5oo6 ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/NCBP1_HUMAN NCBP1_HUMAN]] Component of the cap-binding complex (CBC), which binds cotranscriptionally to the 5'-cap of pre-mRNAs and is involved in various processes such as pre-mRNA splicing, translation regulation, nonsense-mediated mRNA decay, RNA-mediated gene silencing (RNAi) by microRNAs (miRNAs) and mRNA export. The CBC complex is involved in mRNA export from the nucleus via its interaction with ALYREF/THOC4/ALY, leading to the recruitment of the mRNA export machinery to the 5'-end of mRNA and to mRNA export in a 5' to 3' direction through the nuclear pore. The CBC complex is also involved in mediating U snRNA and intronless mRNAs export from the nucleus. The CBC complex is essential for a pioneer round of mRNA translation, before steady state translation when the CBC complex is replaced by cytoplasmic cap-binding protein eIF4E. The pioneer round of mRNA translation mediated by the CBC complex plays a central role in nonsense-mediated mRNA decay (NMD), NMD only taking place in mRNAs bound to the CBC complex, but not on eIF4E-bound mRNAs. The CBC complex enhances NMD in mRNAs containing at least one exon-junction complex (EJC) via its interaction with UPF1, promoting the interaction between UPF1 and UPF2. The CBC complex is also involved in 'failsafe' NMD, which is independent of the EJC complex, while it does not participate in Staufen-mediated mRNA decay (SMD). During cell proliferation, the CBC complex is also involved in microRNAs (miRNAs) biogenesis via its interaction with SRRT/ARS2 and is required for miRNA-mediated RNA interference. The CBC complex also acts as a negative regulator of PARN, thereby acting as an inhibitor of mRNA deadenylation. In the CBC complex, NCBP1/CBP80 does not bind directly capped RNAs (m7GpppG-capped RNA) but is required to stabilize the movement of the N-terminal loop of NCBP2/CBP20 and lock the CBC into a high affinity cap-binding state with the cap structure.<ref>PMID:8069914</ref> <ref>PMID:7651522</ref> <ref>PMID:11551508</ref> <ref>PMID:15059963</ref> <ref>PMID:15361857</ref> <ref>PMID:16186820</ref> <ref>PMID:17190602</ref> <ref>PMID:16317009</ref> <ref>PMID:17873884</ref> <ref>PMID:18369367</ref> <ref>PMID:19632182</ref> <ref>PMID:19648179</ref>  [[http://www.uniprot.org/uniprot/SRRT_HUMAN SRRT_HUMAN]] Acts as a mediator between the cap-binding complex (CBC) and the primary microRNAs (miRNAs) processing machinery during cell proliferation. Contributes to the stability and delivery of capped primary miRNA transcripts to the primary miRNA processing complex containing DGCR8 and DROSHA, thereby playing a role in RNA-mediated gene silencing (RNAi) by miRNAs. Binds capped RNAs (m7GpppG-capped RNA); however interaction is probably mediated via its interaction with NCBP1/CBP80 component of the CBC complex. Involved in cell cycle progression at S phase. Does not directly confer arsenite resistance but rather modulates arsenic sensitivity. Independently of its activity on miRNAs, necessary and sufficient to promote neural stem cell self-renewal. Does so by directly binding SOX2 promoter and positively regulating its transcription (By similarity).<ref>PMID:19632182</ref>  [[http://www.uniprot.org/uniprot/NCBP2_HUMAN NCBP2_HUMAN]] Component of the cap-binding complex (CBC), which binds co-transcriptionally to the 5' cap of pre-mRNAs and is involved in various processes such as pre-mRNA splicing, translation regulation, nonsense-mediated mRNA decay, RNA-mediated gene silencing (RNAi) by microRNAs (miRNAs) and mRNA export. The CBC complex is involved in mRNA export from the nucleus via its interaction with ALYREF/THOC4/ALY, leading to the recruitment of the mRNA export machinery to the 5' end of mRNA and to mRNA export in a 5' to 3' direction through the nuclear pore. The CBC complex is also involved in mediating U snRNA and intronless mRNAs export from the nucleus. The CBC complex is essential for a pioneer round of mRNA translation, before steady state translation when the CBC complex is replaced by cytoplasmic cap-binding protein eIF4E. The pioneer round of mRNA translation mediated by the CBC complex plays a central role in nonsense-mediated mRNA decay (NMD), NMD only taking place in mRNAs bound to the CBC complex, but not on eIF4E-bound mRNAs. The CBC complex enhances NMD in mRNAs containing at least one exon-junction complex (EJC) via its interaction with UPF1, promoting the interaction between UPF1 and UPF2. The CBC complex is also involved in 'failsafe' NMD, which is independent of the EJC complex, while it does not participate in Staufen-mediated mRNA decay (SMD). During cell proliferation, the CBC complex is also involved in microRNAs (miRNAs) biogenesis via its interaction with SRRT/ARS2, thereby being required for miRNA-mediated RNA interference. The CBC complex also acts as a negative regulator of PARN, thereby acting as an inhibitor of mRNA deadenylation. In the CBC complex, NCBP2/CBP20 recognizes and binds capped RNAs (m7GpppG-capped RNA) but requires NCBP1/CBP80 to stabilize the movement of its N-terminal loop and lock the CBC into a high affinity cap-binding state with the cap structure.<ref>PMID:11551508</ref> <ref>PMID:15361857</ref> <ref>PMID:17190602</ref> <ref>PMID:17363367</ref> <ref>PMID:17873884</ref> <ref>PMID:18369367</ref> <ref>PMID:19632182</ref>
+[https://www.uniprot.org/uniprot/NCBP1_HUMAN NCBP1_HUMAN] Component of the cap-binding complex (CBC), which binds cotranscriptionally to the 5'-cap of pre-mRNAs and is involved in various processes such as pre-mRNA splicing, translation regulation, nonsense-mediated mRNA decay, RNA-mediated gene silencing (RNAi) by microRNAs (miRNAs) and mRNA export. The CBC complex is involved in mRNA export from the nucleus via its interaction with ALYREF/THOC4/ALY, leading to the recruitment of the mRNA export machinery to the 5'-end of mRNA and to mRNA export in a 5' to 3' direction through the nuclear pore. The CBC complex is also involved in mediating U snRNA and intronless mRNAs export from the nucleus. The CBC complex is essential for a pioneer round of mRNA translation, before steady state translation when the CBC complex is replaced by cytoplasmic cap-binding protein eIF4E. The pioneer round of mRNA translation mediated by the CBC complex plays a central role in nonsense-mediated mRNA decay (NMD), NMD only taking place in mRNAs bound to the CBC complex, but not on eIF4E-bound mRNAs. The CBC complex enhances NMD in mRNAs containing at least one exon-junction complex (EJC) via its interaction with UPF1, promoting the interaction between UPF1 and UPF2. The CBC complex is also involved in 'failsafe' NMD, which is independent of the EJC complex, while it does not participate in Staufen-mediated mRNA decay (SMD). During cell proliferation, the CBC complex is also involved in microRNAs (miRNAs) biogenesis via its interaction with SRRT/ARS2 and is required for miRNA-mediated RNA interference. The CBC complex also acts as a negative regulator of PARN, thereby acting as an inhibitor of mRNA deadenylation. In the CBC complex, NCBP1/CBP80 does not bind directly capped RNAs (m7GpppG-capped RNA) but is required to stabilize the movement of the N-terminal loop of NCBP2/CBP20 and lock the CBC into a high affinity cap-binding state with the cap structure.<ref>PMID:8069914</ref> <ref>PMID:7651522</ref> <ref>PMID:11551508</ref> <ref>PMID:15059963</ref> <ref>PMID:15361857</ref> <ref>PMID:16186820</ref> <ref>PMID:17190602</ref> <ref>PMID:16317009</ref> <ref>PMID:17873884</ref> <ref>PMID:18369367</ref> <ref>PMID:19632182</ref> <ref>PMID:19648179</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 22: / Line 23: @@
 __TOC__
 </StructureSection>
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Cusack, S]]
+[[Category: Cusack S]]
-[[Category: Schulze, W M]]
+[[Category: Schulze WM]]
-[[Category: Complex nuclear cap-binding complex m7gtp c-terminal peptide from ars2]]
-[[Category: Nuclear protein]]

5oo6

From Proteopedia

Current revision

Complex of human nuclear cap-binding complex with ARS2 C-terminal peptide

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

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