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| | <StructureSection load='3p5t' size='340' side='right'caption='[[3p5t]], [[Resolution|resolution]] 2.70Å' scene=''> | | <StructureSection load='3p5t' size='340' side='right'caption='[[3p5t]], [[Resolution|resolution]] 2.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3p5t]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3P5T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3P5T FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3p5t]] is a 12 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=3P5T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3P5T FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3p6y|3p6y]]</div></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]] 2.7Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NUDT21, CFIM25, CPSF25, CPSF5 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), CPSF6, CFIM68 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=3p5t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3p5t OCA], [https://pdbe.org/3p5t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3p5t RCSB], [https://www.ebi.ac.uk/pdbsum/3p5t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3p5t ProSAT]</span></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=3p5t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3p5t OCA], [https://pdbe.org/3p5t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3p5t RCSB], [https://www.ebi.ac.uk/pdbsum/3p5t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3p5t ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/CPSF5_HUMAN CPSF5_HUMAN]] Component of the cleavage factor Im (CFIm) complex that plays a key role in pre-mRNA 3'-processing. Involved in association with CPSF6 or CPSF7 in pre-MRNA 3'-end poly(A) site cleavage and poly(A) addition. NUDT21/CPSF5 binds to cleavage and polyadenylation RNA substrates. The homodimer mediates simultaneous sequence-specific recognition of two 5'-UGUA-3' elements within the pre-mRNA. Binds to, but does not hydrolyze mono- and di-adenosine nucleotides. May have a role in mRNA export.<ref>PMID:9659921</ref> <ref>PMID:8626397</ref> <ref>PMID:14690600</ref> <ref>PMID:20695905</ref> <ref>PMID:20479262</ref> <ref>PMID:21295486</ref> [[https://www.uniprot.org/uniprot/CPSF6_HUMAN CPSF6_HUMAN]] Component of the cleavage factor Im complex (CFIm) that plays a key role in pre-mRNA 3'-processing. Involved in association with NUDT21/CPSF5 in pre-MRNA 3'-end poly(A) site cleavage and poly(A) addition. CPSF6 binds to cleavage and polyadenylation RNA substrates and promotes RNA looping.<ref>PMID:9659921</ref> <ref>PMID:8626397</ref> <ref>PMID:14690600</ref> <ref>PMID:20695905</ref> <ref>PMID:21295486</ref>
| + | [https://www.uniprot.org/uniprot/CPSF5_HUMAN CPSF5_HUMAN] Component of the cleavage factor Im (CFIm) complex that plays a key role in pre-mRNA 3'-processing. Involved in association with CPSF6 or CPSF7 in pre-MRNA 3'-end poly(A) site cleavage and poly(A) addition. NUDT21/CPSF5 binds to cleavage and polyadenylation RNA substrates. The homodimer mediates simultaneous sequence-specific recognition of two 5'-UGUA-3' elements within the pre-mRNA. Binds to, but does not hydrolyze mono- and di-adenosine nucleotides. May have a role in mRNA export.<ref>PMID:9659921</ref> <ref>PMID:8626397</ref> <ref>PMID:14690600</ref> <ref>PMID:20695905</ref> <ref>PMID:20479262</ref> <ref>PMID:21295486</ref> |
| | + | <div style="background-color:#fffaf0;"> |
| | + | == Publication Abstract from PubMed == |
| | + | The cleavage factor I(m) (CF I(m)), consists of a 25 kDa subunit (CF I(m)25) and one of three larger subunits (CF I(m)59, CF I(m)68, CF I(m)72), and is an essential protein complex for pre-mRNA 3'-end cleavage and polyadenylation. It recognizes the upstream sequence of the poly(A) site in a sequence-dependent manner. Here we report the crystal structure of human CF I(m), comprising CF I(m)25 and the RNA recognition motif domain of CF I(m)68 (CF I(m)68RRM), and the crystal structure of the CF I(m)-RNA complex. These structures show that two CF I(m)68RRM molecules bind to the CF I(m)25 dimer via a novel RRM-protein interaction mode forming a heterotetramer. The RNA-bound structure shows that two UGUAA RNA sequences, with anti-parallel orientation, bind to one CF I(m)25-CF I(m)68RRM heterotetramer, providing structural basis for the mechanism by which CF I(m) binds two UGUAA elements within one molecule of pre-mRNA simultaneously. Point mutation and kinetic analyses demonstrate that CF I(m)68RRM can bind the immediately flanking upstream region of the UGUAA element, and CF I(m)68RRM binding significantly increases the RNA-binding affinity of the complex, suggesting that CF I(m)68 makes an essential contribution to pre-mRNA binding. |
| | + | |
| | + | Structural basis of pre-mRNA recognition by the human cleavage factor Im complex.,Li H, Tong S, Li X, Shi H, Ying Z, Gao Y, Ge H, Niu L, Teng M Cell Res. 2011 Jul;21(7):1039-51. doi: 10.1038/cr.2011.67. Epub 2011 Apr 12. PMID:21483454<ref>PMID:21483454</ref> |
| | + | |
| | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | + | </div> |
| | + | <div class="pdbe-citations 3p5t" style="background-color:#fffaf0;"></div> |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Gao, Y]] | + | [[Category: Gao Y]] |
| - | [[Category: Ge, H]] | + | [[Category: Ge H]] |
| - | [[Category: Li, H]] | + | [[Category: Li H]] |
| - | [[Category: Li, X]] | + | [[Category: Li X]] |
| - | [[Category: Niu, L]] | + | [[Category: Niu L]] |
| - | [[Category: Shi, H]] | + | [[Category: Shi H]] |
| - | [[Category: Teng, M]] | + | [[Category: Teng M]] |
| - | [[Category: Tong, S]] | + | [[Category: Tong S]] |
| - | [[Category: Nuclear]]
| + | |
| - | [[Category: Rna]]
| + | |
| - | [[Category: Rna binding protein]]
| + | |
| - | [[Category: Rrm domain]]
| + | |
| Structural highlights
Function
CPSF5_HUMAN Component of the cleavage factor Im (CFIm) complex that plays a key role in pre-mRNA 3'-processing. Involved in association with CPSF6 or CPSF7 in pre-MRNA 3'-end poly(A) site cleavage and poly(A) addition. NUDT21/CPSF5 binds to cleavage and polyadenylation RNA substrates. The homodimer mediates simultaneous sequence-specific recognition of two 5'-UGUA-3' elements within the pre-mRNA. Binds to, but does not hydrolyze mono- and di-adenosine nucleotides. May have a role in mRNA export.[1] [2] [3] [4] [5] [6]
Publication Abstract from PubMed
The cleavage factor I(m) (CF I(m)), consists of a 25 kDa subunit (CF I(m)25) and one of three larger subunits (CF I(m)59, CF I(m)68, CF I(m)72), and is an essential protein complex for pre-mRNA 3'-end cleavage and polyadenylation. It recognizes the upstream sequence of the poly(A) site in a sequence-dependent manner. Here we report the crystal structure of human CF I(m), comprising CF I(m)25 and the RNA recognition motif domain of CF I(m)68 (CF I(m)68RRM), and the crystal structure of the CF I(m)-RNA complex. These structures show that two CF I(m)68RRM molecules bind to the CF I(m)25 dimer via a novel RRM-protein interaction mode forming a heterotetramer. The RNA-bound structure shows that two UGUAA RNA sequences, with anti-parallel orientation, bind to one CF I(m)25-CF I(m)68RRM heterotetramer, providing structural basis for the mechanism by which CF I(m) binds two UGUAA elements within one molecule of pre-mRNA simultaneously. Point mutation and kinetic analyses demonstrate that CF I(m)68RRM can bind the immediately flanking upstream region of the UGUAA element, and CF I(m)68RRM binding significantly increases the RNA-binding affinity of the complex, suggesting that CF I(m)68 makes an essential contribution to pre-mRNA binding.
Structural basis of pre-mRNA recognition by the human cleavage factor Im complex.,Li H, Tong S, Li X, Shi H, Ying Z, Gao Y, Ge H, Niu L, Teng M Cell Res. 2011 Jul;21(7):1039-51. doi: 10.1038/cr.2011.67. Epub 2011 Apr 12. PMID:21483454[7]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Ruegsegger U, Blank D, Keller W. Human pre-mRNA cleavage factor Im is related to spliceosomal SR proteins and can be reconstituted in vitro from recombinant subunits. Mol Cell. 1998 Jan;1(2):243-53. PMID:9659921
- ↑ Ruegsegger U, Beyer K, Keller W. Purification and characterization of human cleavage factor Im involved in the 3' end processing of messenger RNA precursors. J Biol Chem. 1996 Mar 15;271(11):6107-13. PMID:8626397
- ↑ Brown KM, Gilmartin GM. A mechanism for the regulation of pre-mRNA 3' processing by human cleavage factor Im. Mol Cell. 2003 Dec;12(6):1467-76. PMID:14690600
- ↑ Kim S, Yamamoto J, Chen Y, Aida M, Wada T, Handa H, Yamaguchi Y. Evidence that cleavage factor Im is a heterotetrameric protein complex controlling alternative polyadenylation. Genes Cells. 2010 Sep 1;15(9):1003-13. doi: 10.1111/j.1365-2443.2010.01436.x., Epub 2010 Jul 29. PMID:20695905 doi:10.1111/j.1365-2443.2010.01436.x
- ↑ Yang Q, Gilmartin GM, Doublie S. Structural basis of UGUA recognition by the Nudix protein CFI(m)25 and implications for a regulatory role in mRNA 3' processing. Proc Natl Acad Sci U S A. 2010 Jun 1;107(22):10062-7. Epub 2010 May 17. PMID:20479262
- ↑ Yang Q, Coseno M, Gilmartin GM, Doublie S. Crystal Structure of a Human Cleavage Factor CFI(m)25/CFI(m)68/RNA Complex Provides an Insight into Poly(A) Site Recognition and RNA Looping. Structure. 2011 Feb 2. PMID:21295486 doi:10.1016/j.str.2010.12.021
- ↑ Li H, Tong S, Li X, Shi H, Ying Z, Gao Y, Ge H, Niu L, Teng M. Structural basis of pre-mRNA recognition by the human cleavage factor Im complex. Cell Res. 2011 Jul;21(7):1039-51. PMID:21483454 doi:10.1038/cr.2011.67
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