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| | ==Crystal structure of human Acinus RNA recognition motif domain== | | ==Crystal structure of human Acinus RNA recognition motif domain== |
| - | <StructureSection load='6g6s' size='340' side='right' caption='[[6g6s]], [[Resolution|resolution]] 1.65Å' scene=''> | + | <StructureSection load='6g6s' size='340' side='right'caption='[[6g6s]], [[Resolution|resolution]] 1.65Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6g6s]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6G6S OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6G6S FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6g6s]] is a 2 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=6G6S OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6G6S FirstGlance]. <br> |
| - | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6g6s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6g6s OCA], [http://pdbe.org/6g6s PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6g6s RCSB], [http://www.ebi.ac.uk/pdbsum/6g6s PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6g6s ProSAT]</span></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]] 1.65Å</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=6g6s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6g6s OCA], [https://pdbe.org/6g6s PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6g6s RCSB], [https://www.ebi.ac.uk/pdbsum/6g6s PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6g6s ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/ACINU_HUMAN ACINU_HUMAN]] Auxiliary component of the splicing-dependent multiprotein exon junction complex (EJC) deposited at splice junction on mRNAs. The EJC is a dynamic structure consisting of core proteins and several peripheral nuclear and cytoplasmic associated factors that join the complex only transiently either during EJC assembly or during subsequent mRNA metabolism. Component of the ASAP complexes which bind RNA in a sequence-independent manner and are proposed to be recruited to the EJC prior to or during the splicing process and to regulate specific excision of introns in specific transcription subsets; ACIN1 confers RNA-binding to the complex. The ASAP complex can inhibit RNA processing during in vitro splicing reactions. The ASAP complex promotes apoptosis and is disassembled after induction of apoptosis. Involved in the splicing modulation of BCL2L1/Bcl-X (and probably other apoptotic genes); specifically inhibits formation of proapoptotic isoforms such as Bcl-X(S); the activity is different from the established EJC assembly and function. Induces apoptotic chromatin condensation after activation by CASP3. Regulates cyclin A1, but not cyclin A2, expression in leukemia cells.<ref>PMID:10490026</ref> <ref>PMID:12665594</ref> <ref>PMID:18559500</ref> <ref>PMID:22203037</ref> <ref>PMID:22388736</ref> | + | [https://www.uniprot.org/uniprot/ACINU_HUMAN ACINU_HUMAN] Auxiliary component of the splicing-dependent multiprotein exon junction complex (EJC) deposited at splice junction on mRNAs. The EJC is a dynamic structure consisting of core proteins and several peripheral nuclear and cytoplasmic associated factors that join the complex only transiently either during EJC assembly or during subsequent mRNA metabolism. Component of the ASAP complexes which bind RNA in a sequence-independent manner and are proposed to be recruited to the EJC prior to or during the splicing process and to regulate specific excision of introns in specific transcription subsets; ACIN1 confers RNA-binding to the complex. The ASAP complex can inhibit RNA processing during in vitro splicing reactions. The ASAP complex promotes apoptosis and is disassembled after induction of apoptosis. Involved in the splicing modulation of BCL2L1/Bcl-X (and probably other apoptotic genes); specifically inhibits formation of proapoptotic isoforms such as Bcl-X(S); the activity is different from the established EJC assembly and function. Induces apoptotic chromatin condensation after activation by CASP3. Regulates cyclin A1, but not cyclin A2, expression in leukemia cells.<ref>PMID:10490026</ref> <ref>PMID:12665594</ref> <ref>PMID:18559500</ref> <ref>PMID:22203037</ref> <ref>PMID:22388736</ref> |
| | + | <div style="background-color:#fffaf0;"> |
| | + | == Publication Abstract from PubMed == |
| | + | Acinus is an abundant nuclear protein involved in apoptosis and splicing. It has been implicated in inducing apoptotic chromatin condensation and DNA fragmentation during programmed cell death. Acinus undergoes activation by proteolytic cleavage that produces a truncated p17 form that comprises only the RNA recognition motif (RRM) domain. We have determined the crystal structure of the human Acinus RRM domain (AcRRM) at 1.65 A resolution. It shows a classical four-stranded antiparallel beta-sheet fold with two flanking alpha-helices and an additional, non-classical alpha-helix at the C-terminus, which harbors the caspase-3 target sequence that is cleaved during Acinus activation. In the structure, the C-terminal alpha-helix partially occludes the potential ligand binding surface of the beta-sheet and hypothetically shields it from non-sequence specific interactions with RNA. Based on the comparison with other RRM-RNA complex structures, it is likely that the C-terminal alpha-helix changes its conformation with respect to the RRM core in order to enable RNA binding by Acinus. |
| | + | |
| | + | Crystal structure of human Acinus RNA recognition motif domain.,Fernandes H, Czapinska H, Grudziaz K, Bujnicki JM, Nowacka M PeerJ. 2018 Jul 4;6:e5163. doi: 10.7717/peerj.5163. eCollection 2018. PMID:30042883<ref>PMID:30042883</ref> |
| | + | |
| | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | + | </div> |
| | + | <div class="pdbe-citations 6g6s" style="background-color:#fffaf0;"></div> |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Bujnicki, J M]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Czapinska, H]] | + | [[Category: Large Structures]] |
| - | [[Category: Fernandes, H]] | + | [[Category: Bujnicki JM]] |
| - | [[Category: Grudziaz, K]] | + | [[Category: Czapinska H]] |
| - | [[Category: Nowacka, M]] | + | [[Category: Fernandes H]] |
| - | [[Category: Acinus]] | + | [[Category: Grudziaz K]] |
| - | [[Category: Apoptosis]] | + | [[Category: Nowacka M]] |
| - | [[Category: Rna binding protein]]
| + | |
| - | [[Category: Rrm domain]]
| + | |
| - | [[Category: Splicing factor]]
| + | |
| Structural highlights
Function
ACINU_HUMAN Auxiliary component of the splicing-dependent multiprotein exon junction complex (EJC) deposited at splice junction on mRNAs. The EJC is a dynamic structure consisting of core proteins and several peripheral nuclear and cytoplasmic associated factors that join the complex only transiently either during EJC assembly or during subsequent mRNA metabolism. Component of the ASAP complexes which bind RNA in a sequence-independent manner and are proposed to be recruited to the EJC prior to or during the splicing process and to regulate specific excision of introns in specific transcription subsets; ACIN1 confers RNA-binding to the complex. The ASAP complex can inhibit RNA processing during in vitro splicing reactions. The ASAP complex promotes apoptosis and is disassembled after induction of apoptosis. Involved in the splicing modulation of BCL2L1/Bcl-X (and probably other apoptotic genes); specifically inhibits formation of proapoptotic isoforms such as Bcl-X(S); the activity is different from the established EJC assembly and function. Induces apoptotic chromatin condensation after activation by CASP3. Regulates cyclin A1, but not cyclin A2, expression in leukemia cells.[1] [2] [3] [4] [5]
Publication Abstract from PubMed
Acinus is an abundant nuclear protein involved in apoptosis and splicing. It has been implicated in inducing apoptotic chromatin condensation and DNA fragmentation during programmed cell death. Acinus undergoes activation by proteolytic cleavage that produces a truncated p17 form that comprises only the RNA recognition motif (RRM) domain. We have determined the crystal structure of the human Acinus RRM domain (AcRRM) at 1.65 A resolution. It shows a classical four-stranded antiparallel beta-sheet fold with two flanking alpha-helices and an additional, non-classical alpha-helix at the C-terminus, which harbors the caspase-3 target sequence that is cleaved during Acinus activation. In the structure, the C-terminal alpha-helix partially occludes the potential ligand binding surface of the beta-sheet and hypothetically shields it from non-sequence specific interactions with RNA. Based on the comparison with other RRM-RNA complex structures, it is likely that the C-terminal alpha-helix changes its conformation with respect to the RRM core in order to enable RNA binding by Acinus.
Crystal structure of human Acinus RNA recognition motif domain.,Fernandes H, Czapinska H, Grudziaz K, Bujnicki JM, Nowacka M PeerJ. 2018 Jul 4;6:e5163. doi: 10.7717/peerj.5163. eCollection 2018. PMID:30042883[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Sahara S, Aoto M, Eguchi Y, Imamoto N, Yoneda Y, Tsujimoto Y. Acinus is a caspase-3-activated protein required for apoptotic chromatin condensation. Nature. 1999 Sep 9;401(6749):168-73. doi: 10.1038/43678. PMID:10490026 doi:http://dx.doi.org/10.1038/43678
- ↑ Schwerk C, Prasad J, Degenhardt K, Erdjument-Bromage H, White E, Tempst P, Kidd VJ, Manley JL, Lahti JM, Reinberg D. ASAP, a novel protein complex involved in RNA processing and apoptosis. Mol Cell Biol. 2003 Apr;23(8):2981-90. PMID:12665594
- ↑ Jang SW, Yang SJ, Ehlen A, Dong S, Khoury H, Chen J, Persson JL, Ye K. Serine/arginine protein-specific kinase 2 promotes leukemia cell proliferation by phosphorylating acinus and regulating cyclin A1. Cancer Res. 2008 Jun 15;68(12):4559-70. doi: 10.1158/0008-5472.CAN-08-0021. PMID:18559500 doi:http://dx.doi.org/10.1158/0008-5472.CAN-08-0021
- ↑ Michelle L, Cloutier A, Toutant J, Shkreta L, Thibault P, Durand M, Garneau D, Gendron D, Lapointe E, Couture S, Le Hir H, Klinck R, Elela SA, Prinos P, Chabot B. Proteins associated with the exon junction complex also control the alternative splicing of apoptotic regulators. Mol Cell Biol. 2012 Mar;32(5):954-67. doi: 10.1128/MCB.06130-11. Epub 2011 Dec, 27. PMID:22203037 doi:http://dx.doi.org/10.1128/MCB.06130-11
- ↑ Murachelli AG, Ebert J, Basquin C, Le Hir H, Conti E. The structure of the ASAP core complex reveals the existence of a Pinin-containing PSAP complex. Nat Struct Mol Biol. 2012 Mar 4;19(4):378-86. doi: 10.1038/nsmb.2242. PMID:22388736 doi:10.1038/nsmb.2242
- ↑ Fernandes H, Czapinska H, Grudziaz K, Bujnicki JM, Nowacka M. Crystal structure of human Acinus RNA recognition motif domain. PeerJ. 2018 Jul 4;6:e5163. doi: 10.7717/peerj.5163. eCollection 2018. PMID:30042883 doi:http://dx.doi.org/10.7717/peerj.5163
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