2lkz

From Proteopedia

(Difference between revisions)

Revision as of 20:19, 25 December 2014

Solution structure of the second RRM domain of RBM5

Structural highlights

2lkz is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	RBM5, H37, LUCA15 (Homo sapiens)
Resources:	FirstGlance, OCA, RCSB, PDBsum

Function

[RBM5_HUMAN] Component of the spliceosome A complex. Regulates alternative splicing of a number of mRNAs. May modulate splice site pairing after recruitment of the U1 and U2 snRNPs to the 5' and 3' splice sites of the intron. May both positively and negatively regulate aopotosis by regulating the alternative splicing of several genes involved in this process, including FAS and CASP2/caspase-2. In the case of FAS, promotes exclusion of exon 6 thereby producing a soluble form of FAS that inhibits apoptosis. In the case of CASP2/caspase-2, promotes exclusion of exon 9 thereby producing a catalytically active form of CASP2/Caspase-2 that induces apoptosis.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7]

Publication Abstract from PubMed

The RNA binding motif protein 5 (RBM5), also known as LUCA15 or H37, containing two RNA recognition motifs, is a component of the spliceosome A complex. Previously, it has been reported that RBM5 bound to a U/C-rich sequence upstream of In100 element at intron 9 of caspase2 pre-mRNA that enhanced the formation of proapoptotic caspase-2L isoform. In present studies, we solved the solution structure of the RBM5 RRM2 core domain and characterized its unusual binding capability for different RNA sequences. We found that the RBM5 RRM2 could preferentially bind to both CU rich and GA rich sequences with affinity in 10-5 molar range. Further NMR experiments revealed that the dual RNA molecules could be accommodated on almost the same region of the protein's beta-sheet surface and both the N- and C-terminal regions of the protein were involved in the recognition. Our studies provide evidence for RBM5 sequence specific interaction with cis-acting element in pre-mRNA to regulate alternative splicing.

Solution structure of the second RRM domain of RBM5 and its unusual binding characters for different RNA targets.,Song Z, Wu P, Ji P, Zhang J, Gong Q, Wu J, Shi Y Biochemistry. 2012 Jul 27. PMID:22839758^[8]

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

References

↑ Sutherland LC, Edwards SE, Cable HC, Poirier GG, Miller BA, Cooper CS, Williams GT. LUCA-15-encoded sequence variants regulate CD95-mediated apoptosis. Oncogene. 2000 Aug 3;19(33):3774-81. PMID:10949932 doi:http://dx.doi.org/10.1038/sj.onc.1203720
↑ Mourtada-Maarabouni M, Sutherland LC, Williams GT. Candidate tumour suppressor LUCA-15 can regulate multiple apoptotic pathways. Apoptosis. 2002 Oct;7(5):421-32. PMID:12207175
↑ Mourtada-Maarabouni M, Sutherland LC, Meredith JM, Williams GT. Simultaneous acceleration of the cell cycle and suppression of apoptosis by splice variant delta-6 of the candidate tumour suppressor LUCA-15/RBM5. Genes Cells. 2003 Feb;8(2):109-19. PMID:12581154
↑ Rintala-Maki ND, Sutherland LC. LUCA-15/RBM5, a putative tumour suppressor, enhances multiple receptor-initiated death signals. Apoptosis. 2004 Jul;9(4):475-84. PMID:15192330 doi:http://dx.doi.org/10.1023/B:APPT.0000031455.79352.57
↑ Oh JJ, Razfar A, Delgado I, Reed RA, Malkina A, Boctor B, Slamon DJ. 3p21.3 tumor suppressor gene H37/Luca15/RBM5 inhibits growth of human lung cancer cells through cell cycle arrest and apoptosis. Cancer Res. 2006 Apr 1;66(7):3419-27. PMID:16585163 doi:http://dx.doi.org/66/7/3419
↑ Bonnal S, Martinez C, Forch P, Bachi A, Wilm M, Valcarcel J. RBM5/Luca-15/H37 regulates Fas alternative splice site pairing after exon definition. Mol Cell. 2008 Oct 10;32(1):81-95. doi: 10.1016/j.molcel.2008.08.008. PMID:18851835 doi:http://dx.doi.org/10.1016/j.molcel.2008.08.008
↑ Fushimi K, Ray P, Kar A, Wang L, Sutherland LC, Wu JY. Up-regulation of the proapoptotic caspase 2 splicing isoform by a candidate tumor suppressor, RBM5. Proc Natl Acad Sci U S A. 2008 Oct 14;105(41):15708-13. doi:, 10.1073/pnas.0805569105. Epub 2008 Oct 7. PMID:18840686 doi:http://dx.doi.org/10.1073/pnas.0805569105
↑ Song Z, Wu P, Ji P, Zhang J, Gong Q, Wu J, Shi Y. Solution structure of the second RRM domain of RBM5 and its unusual binding characters for different RNA targets. Biochemistry. 2012 Jul 27. PMID:22839758 doi:10.1021/bi300539t

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/2lkz"

@@ Line 6: / Line 6: @@
 <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=2lkz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2lkz OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2lkz RCSB], [http://www.ebi.ac.uk/pdbsum/2lkz PDBsum]</span></td></tr>
 </table>
+== Function ==
+[[http://www.uniprot.org/uniprot/RBM5_HUMAN RBM5_HUMAN]] Component of the spliceosome A complex. Regulates alternative splicing of a number of mRNAs. May modulate splice site pairing after recruitment of the U1 and U2 snRNPs to the 5' and 3' splice sites of the intron. May both positively and negatively regulate aopotosis by regulating the alternative splicing of several genes involved in this process, including FAS and CASP2/caspase-2. In the case of FAS, promotes exclusion of exon 6 thereby producing a soluble form of FAS that inhibits apoptosis. In the case of CASP2/caspase-2, promotes exclusion of exon 9 thereby producing a catalytically active form of CASP2/Caspase-2 that induces apoptosis.<ref>PMID:10949932</ref> <ref>PMID:12207175</ref> <ref>PMID:12581154</ref> <ref>PMID:15192330</ref> <ref>PMID:16585163</ref> <ref>PMID:18851835</ref> <ref>PMID:18840686</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==

2lkz

From Proteopedia

Revision as of 20:19, 25 December 2014

Solution structure of the second RRM domain of RBM5

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox