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2i7v

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Revision as of 08:24, 18 October 2017

Structure of Human CPSF-73

Structural highlights

2i7v is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	2i7t, 2i7x
Gene:	CPSF3, CPSF73 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[CPSF3_HUMAN] Component of the cleavage and polyadenylation specificity factor (CPSF) complex that play a key role in pre-mRNA 3'-end formation, recognizing the AAUAAA signal sequence and interacting with poly(A) polymerase and other factors to bring about cleavage and poly(A) addition. Has endonuclease activity, and functions as mRNA 3'-end-processing endonuclease. Also involved in the histone 3'-end pre-mRNA processing. U7 snRNP-dependent protein that induces both the 3'-endoribonucleolytic cleavage of histone pre-mRNAs and acts as a 5' to 3' exonuclease for degrading the subsequent downstream cleavage product (DCP) of mature histone mRNAs. Cleavage occurs after the 5'-ACCCA-3' sequence in the histone pre-mRNA leaving a 3'hydroxyl group on the upstream fragment containing the stem loop (SL) and 5' phosphate on the downstream cleavage product (DCP) starting with CU nucleotides. The U7-dependent 5' to 3' exonuclease activity is processive and degrades the DCP RNA substrate even after complete removal of the U7-binding site. Binds to the downstream cleavage product (DCP) of histone pre-mRNAs and the cleaved DCP RNA substrate in a U7 snRNP dependent manner.^[1] ^[2] ^[3] ^[4]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Most eukaryotic messenger RNA precursors (pre-mRNAs) undergo extensive maturational processing, including cleavage and polyadenylation at the 3'-end. Despite the characterization of many proteins that are required for the cleavage reaction, the identity of the endonuclease is not known. Recent analyses indicated that the 73-kDa subunit of cleavage and polyadenylation specificity factor (CPSF-73) might be the endonuclease for this and related reactions, although no direct data confirmed this. Here we report the crystal structures of human CPSF-73 at 2.1 A resolution, complexed with zinc ions and a sulphate that might mimic the phosphate group of the substrate, and the related yeast protein CPSF-100 (Ydh1) at 2.5 A resolution. Both CPSF-73 and CPSF-100 contain two domains, a metallo-beta-lactamase domain and a novel beta-CASP (named for metallo-beta-lactamase, CPSF, Artemis, Snm1, Pso2) domain. The active site of CPSF-73, with two zinc ions, is located at the interface of the two domains. Purified recombinant CPSF-73 possesses RNA endonuclease activity, and mutations that disrupt zinc binding in the active site abolish this activity. Our studies provide the first direct experimental evidence that CPSF-73 is the pre-mRNA 3'-end-processing endonuclease.

Polyadenylation factor CPSF-73 is the pre-mRNA 3'-end-processing endonuclease.,Mandel CR, Kaneko S, Zhang H, Gebauer D, Vethantham V, Manley JL, Tong L Nature. 2006 Dec 14;444(7121):953-6. Epub 2006 Nov 26. PMID:17128255^[5]

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

References

↑ Kaufmann I, Martin G, Friedlein A, Langen H, Keller W. Human Fip1 is a subunit of CPSF that binds to U-rich RNA elements and stimulates poly(A) polymerase. EMBO J. 2004 Feb 11;23(3):616-26. Epub 2004 Jan 29. PMID:14749727 doi:http://dx.doi.org/10.1038/sj.emboj.7600070
↑ Ryan K, Calvo O, Manley JL. Evidence that polyadenylation factor CPSF-73 is the mRNA 3' processing endonuclease. RNA. 2004 Apr;10(4):565-73. PMID:15037765
↑ Kolev NG, Yario TA, Benson E, Steitz JA. Conserved motifs in both CPSF73 and CPSF100 are required to assemble the active endonuclease for histone mRNA 3'-end maturation. EMBO Rep. 2008 Oct;9(10):1013-8. doi: 10.1038/embor.2008.146. Epub 2008 Aug 8. PMID:18688255 doi:http://dx.doi.org/10.1038/embor.2008.146
↑ Mandel CR, Kaneko S, Zhang H, Gebauer D, Vethantham V, Manley JL, Tong L. Polyadenylation factor CPSF-73 is the pre-mRNA 3'-end-processing endonuclease. Nature. 2006 Dec 14;444(7121):953-6. Epub 2006 Nov 26. PMID:17128255 doi:10.1038/nature05363
↑ Mandel CR, Kaneko S, Zhang H, Gebauer D, Vethantham V, Manley JL, Tong L. Polyadenylation factor CPSF-73 is the pre-mRNA 3'-end-processing endonuclease. Nature. 2006 Dec 14;444(7121):953-6. Epub 2006 Nov 26. PMID:17128255 doi:10.1038/nature05363

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2i7v"

@@ Line 1: / Line 1: @@
 ==Structure of Human CPSF-73==
 <StructureSection load='2i7v' size='340' side='right' caption='[[2i7v]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
@@ Line 6: / Line 7: @@
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2i7t|2i7t]], [[2i7x|2i7x]]</td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CPSF3, CPSF73 ([http://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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2i7v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2i7v OCA], [http://pdbe.org/2i7v PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2i7v RCSB], [http://www.ebi.ac.uk/pdbsum/2i7v PDBsum]</span></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=2i7v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2i7v OCA], [http://pdbe.org/2i7v PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2i7v RCSB], [http://www.ebi.ac.uk/pdbsum/2i7v PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2i7v ProSAT]</span></td></tr>
 </table>
 == Function ==

2i7v

From Proteopedia

Revision as of 08:24, 18 October 2017

Structure of Human CPSF-73

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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