5ytv

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of YB1 cold-shock domain in complex with UCAUCU

Structural highlights

5ytv is a 2 chain structure with sequence from Homo sapiens and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.7Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

YBOX1_HUMAN Mediates pre-mRNA alternative splicing regulation. Binds to splice sites in pre-mRNA and regulates splice site selection. Binds and stabilizes cytoplasmic mRNA. Contributes to the regulation of translation by modulating the interaction between the mRNA and eukaryotic initiation factors (By similarity). Regulates the transcription of numerous genes. Its transcriptional activity on the multidrug resistance gene MDR1 is enhanced in presence of the APEX1 acetylated form at 'Lys-6' and 'Lys-7'. Binds to promoters that contain a Y-box (5'-CTGATTGGCCAA-3'), such as MDR1 and HLA class II genes. Promotes separation of DNA strands that contain mismatches or are modified by cisplatin. Has endonucleolytic activity and can introduce nicks or breaks into double-stranded DNA (in vitro). May play a role in DNA repair. Component of the CRD-mediated complex that promotes MYC mRNA stability. Binds preferentially to the 5'-[CU]CUGCG-3' motif in vitro.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8] The secreted form acts as an extracellular mitogen and stimulates cell migration and proliferation.

Publication Abstract from PubMed

The Y-box binding protein 1 (YB-1) is a member of the cold shock domain (CSD) protein family and is recognized as an oncogenic factor in several solid tumors. By binding to RNA, YB-1 participates in several steps of posttranscriptional regulation of gene expression, including mRNA splicing, stability, and translation; microRNA (miRNA) processing; and stress granule assembly. However, the mechanisms in YB-1-mediated regulation of RNAs are unclear. Previously, we used both systematic evolution of ligands by exponential enrichment (SELEX) and individual-nucleotide resolution UV crosslinking and immunoprecipitation coupled RNA-seq (iCLIP-seq) analyses, which defined the RNA-binding consensus sequence of YB-1 as CA(U/C)C. We also reported that through binding to its core motif CAUC in primary transcripts, YB-1 regulates the alternative splicing of a CD44 variable exon and the biogenesis of miR-29b-2 during both Drosha and Dicer steps. To elucidate the molecular basis of the YB-1-RNA interactions, we report high-resolution crystal structures of the YB-1 CSD in complex with different RNA oligos at 1.7 A resolution. The structure revealed that CSD interacts with RNA mainly through pi-pi stacking interactions assembled by four highly conserved aromatic residues. Interestingly, YB-1 CSD forms a homodimer in solution, and we observed that two residues, Tyr-99 and Asp-105, at the dimer interface are important for YB-1 CSD dimerization. Substituting these two residues with Ala reduced CSD's RNA binding activity and abrogated the splicing activation of YB-1 targets. The YB-1 CSD-RNA structures presented here at atomic resolution provide mechanistic insights into gene expression regulated by CSD-containing proteins.

Crystal structure of a Y-box binding protein 1 (YB-1)-RNA complex reveals key features and residues interacting with RNA.,Yang XJ, Zhu H, Mu SR, Wei WJ, Yuan X, Wang M, Liu Y, Hui J, Huang Y J Biol Chem. 2019 Jun 3. pii: RA119.007545. doi: 10.1074/jbc.RA119.007545. PMID:31160337^[9]

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

References

↑ Chen CY, Gherzi R, Andersen JS, Gaietta G, Jurchott K, Royer HD, Mann M, Karin M. Nucleolin and YB-1 are required for JNK-mediated interleukin-2 mRNA stabilization during T-cell activation. Genes Dev. 2000 May 15;14(10):1236-48. PMID:10817758
↑ Capowski EE, Esnault S, Bhattacharya S, Malter JS. Y box-binding factor promotes eosinophil survival by stabilizing granulocyte-macrophage colony-stimulating factor mRNA. J Immunol. 2001 Nov 15;167(10):5970-6. PMID:11698476
↑ Raffetseder U, Frye B, Rauen T, Jurchott K, Royer HD, Jansen PL, Mertens PR. Splicing factor SRp30c interaction with Y-box protein-1 confers nuclear YB-1 shuttling and alternative splice site selection. J Biol Chem. 2003 May 16;278(20):18241-8. doi: 10.1074/jbc.M212518200. Epub 2003 , Feb 25. PMID:12604611 doi:http://dx.doi.org/10.1074/jbc.M212518200
↑ Gaudreault I, Guay D, Lebel M. YB-1 promotes strand separation in vitro of duplex DNA containing either mispaired bases or cisplatin modifications, exhibits endonucleolytic activities and binds several DNA repair proteins. Nucleic Acids Res. 2004 Jan 12;32(1):316-27. doi: 10.1093/nar/gkh170. Print 2004. PMID:14718551 doi:http://dx.doi.org/10.1093/nar/gkh170
↑ Onishi H, Kino Y, Morita T, Futai E, Sasagawa N, Ishiura S. MBNL1 associates with YB-1 in cytoplasmic stress granules. J Neurosci Res. 2008 Jul;86(9):1994-2002. doi: 10.1002/jnr.21655. PMID:18335541 doi:10.1002/jnr.21655
↑ Chattopadhyay R, Das S, Maiti AK, Boldogh I, Xie J, Hazra TK, Kohno K, Mitra S, Bhakat KK. Regulatory role of human AP-endonuclease (APE1/Ref-1) in YB-1-mediated activation of the multidrug resistance gene MDR1. Mol Cell Biol. 2008 Dec;28(23):7066-80. doi: 10.1128/MCB.00244-08. Epub 2008 Sep , 22. PMID:18809583 doi:10.1128/MCB.00244-08
↑ Weidensdorfer D, Stohr N, Baude A, Lederer M, Kohn M, Schierhorn A, Buchmeier S, Wahle E, Huttelmaier S. Control of c-myc mRNA stability by IGF2BP1-associated cytoplasmic RNPs. RNA. 2009 Jan;15(1):104-15. doi: 10.1261/rna.1175909. Epub 2008 Nov 24. PMID:19029303 doi:10.1261/rna.1175909
↑ Frye BC, Halfter S, Djudjaj S, Muehlenberg P, Weber S, Raffetseder U, En-Nia A, Knott H, Baron JM, Dooley S, Bernhagen J, Mertens PR. Y-box protein-1 is actively secreted through a non-classical pathway and acts as an extracellular mitogen. EMBO Rep. 2009 Jul;10(7):783-9. doi: 10.1038/embor.2009.81. Epub 2009 May 29. PMID:19483673 doi:http://dx.doi.org/10.1038/embor.2009.81
↑ Yang XJ, Zhu H, Mu SR, Wei WJ, Yuan X, Wang M, Liu Y, Hui J, Huang Y. Crystal structure of a Y-box binding protein 1 (YB-1)-RNA complex reveals key features and residues interacting with RNA. J Biol Chem. 2019 Jun 3. pii: RA119.007545. doi: 10.1074/jbc.RA119.007545. PMID:31160337 doi:http://dx.doi.org/10.1074/jbc.RA119.007545

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/5ytv"

Categories: Homo sapiens | Large Structures | Synthetic construct | Huang Y | Yang X

@@ Line 3: / Line 3: @@
 <StructureSection load='5ytv' size='340' side='right'caption='[[5ytv]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5ytv]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5YTV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5YTV FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5ytv]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5YTV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5YTV FirstGlance]. <br>
-</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5yts|5yts]], [[5ytt|5ytt]], [[5ytx|5ytx]]</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]] 1.7&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">YBX1, NSEP1, YB1 ([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'>[https://proteopedia.org/fgij/fg.htm?mol=5ytv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ytv OCA], [https://pdbe.org/5ytv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ytv RCSB], [https://www.ebi.ac.uk/pdbsum/5ytv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ytv ProSAT]</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=5ytv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ytv OCA], [http://pdbe.org/5ytv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ytv RCSB], [http://www.ebi.ac.uk/pdbsum/5ytv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ytv ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/YBOX1_HUMAN YBOX1_HUMAN]] Mediates pre-mRNA alternative splicing regulation. Binds to splice sites in pre-mRNA and regulates splice site selection. Binds and stabilizes cytoplasmic mRNA. Contributes to the regulation of translation by modulating the interaction between the mRNA and eukaryotic initiation factors (By similarity). Regulates the transcription of numerous genes. Its transcriptional activity on the multidrug resistance gene MDR1 is enhanced in presence of the APEX1 acetylated form at 'Lys-6' and 'Lys-7'. Binds to promoters that contain a Y-box (5'-CTGATTGGCCAA-3'), such as MDR1 and HLA class II genes. Promotes separation of DNA strands that contain mismatches or are modified by cisplatin. Has endonucleolytic activity and can introduce nicks or breaks into double-stranded DNA (in vitro). May play a role in DNA repair. Component of the CRD-mediated complex that promotes MYC mRNA stability. Binds preferentially to the 5'-[CU]CUGCG-3' motif in vitro.<ref>PMID:10817758</ref> <ref>PMID:11698476</ref> <ref>PMID:12604611</ref> <ref>PMID:14718551</ref> <ref>PMID:18335541</ref> <ref>PMID:18809583</ref> <ref>PMID:19029303</ref> <ref>PMID:19483673</ref>   The secreted form acts as an extracellular mitogen and stimulates cell migration and proliferation.
+[https://www.uniprot.org/uniprot/YBOX1_HUMAN YBOX1_HUMAN] Mediates pre-mRNA alternative splicing regulation. Binds to splice sites in pre-mRNA and regulates splice site selection. Binds and stabilizes cytoplasmic mRNA. Contributes to the regulation of translation by modulating the interaction between the mRNA and eukaryotic initiation factors (By similarity). Regulates the transcription of numerous genes. Its transcriptional activity on the multidrug resistance gene MDR1 is enhanced in presence of the APEX1 acetylated form at 'Lys-6' and 'Lys-7'. Binds to promoters that contain a Y-box (5'-CTGATTGGCCAA-3'), such as MDR1 and HLA class II genes. Promotes separation of DNA strands that contain mismatches or are modified by cisplatin. Has endonucleolytic activity and can introduce nicks or breaks into double-stranded DNA (in vitro). May play a role in DNA repair. Component of the CRD-mediated complex that promotes MYC mRNA stability. Binds preferentially to the 5'-[CU]CUGCG-3' motif in vitro.<ref>PMID:10817758</ref> <ref>PMID:11698476</ref> <ref>PMID:12604611</ref> <ref>PMID:14718551</ref> <ref>PMID:18335541</ref> <ref>PMID:18809583</ref> <ref>PMID:19029303</ref> <ref>PMID:19483673</ref>   The secreted form acts as an extracellular mitogen and stimulates cell migration and proliferation.
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 23: / Line 22: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Huang, Y]]
+[[Category: Synthetic construct]]
-[[Category: Yang, X]]
+[[Category: Huang Y]]
-[[Category: Cauc]]
+[[Category: Yang X]]
-[[Category: Cold-shock domain]]
-[[Category: Rna binding protein]]
-[[Category: Rna binding protein-rna complex]]
-[[Category: Yb1]]

5ytv

From Proteopedia

Current revision

Crystal structure of YB1 cold-shock domain in complex with UCAUCU

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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