8bgf
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==NMR solution structure of the N-terminal RRM and flanking linker regions of Polypyrimidine tract binding protein 1 using the CYANA CONSENSUS method.== | |
| + | <StructureSection load='8bgf' size='340' side='right'caption='[[8bgf]]' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[8bgf]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8BGF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8BGF FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 20 models</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=8bgf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8bgf OCA], [https://pdbe.org/8bgf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8bgf RCSB], [https://www.ebi.ac.uk/pdbsum/8bgf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8bgf ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/PTBP1_HUMAN PTBP1_HUMAN] Plays a role in pre-mRNA splicing and in the regulation of alternative splicing events. Activates exon skipping of its own pre-mRNA during muscle cell differentiation. Binds to the polypyrimidine tract of introns. May promote RNA looping when bound to two separate polypyrimidine tracts in the same pre-mRNA. May promote the binding of U2 snRNP to pre-mRNA. Cooperates with RAVER1 to modulate switching between mutually exclusive exons during maturation of the TPM1 pre-mRNA. Represses the splicing of MAPT/Tau exon 10.<ref>PMID:11003644</ref> <ref>PMID:15009664</ref> <ref>PMID:16260624</ref> <ref>PMID:21518792</ref> <ref>PMID:16179478</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The N-terminal RNA recognition motif domain (RRM1) of polypyrimidine tract binding protein (PTB) forms an additional C-terminal helix alpha3, which docks to one edge of the beta-sheet upon binding to a stem-loop RNA containing a UCUUU pentaloop. Importantly, alpha3 does not contact the RNA. The alpha3 helix therefore represents an allosteric means to regulate the conformation of adjacent domains in PTB upon binding structured RNAs. Here we investigate the process of dynamic adaptation by stem-loop RNA and RRM1 using NMR and MD in order to obtain mechanistic insights on how this allostery is achieved. Relaxation data and NMR structure determination of the free protein show that alpha3 is partially ordered and interacts with the domain transiently. Stem-loop RNA binding quenches fast time scale dynamics and alpha3 becomes ordered, however microsecond dynamics at the protein-RNA interface is observed. MD shows how RRM1 binding to the stem-loop RNA is coupled to the stabilization of the C-terminal helix and helps to transduce differences in RNA loop sequence into changes in alpha3 length and order. IRES assays of full length PTB and a mutant with altered dynamics in the alpha3 region show that this dynamic allostery influences PTB function in cultured HEK293T cells. | ||
| - | + | N-terminal domain of polypyrimidine-tract binding protein is a dynamic folding platform for adaptive RNA recognition.,Damberger FF, Krepl M, Arora R, Beusch I, Maris C, Dorn G, Sponer J, Ravindranathan S, Allain FH Nucleic Acids Res. 2024 Aug 24:gkae713. doi: 10.1093/nar/gkae713. PMID:39180402<ref>PMID:39180402</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 8bgf" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Allain FH-T]] | ||
| + | [[Category: Beusch I]] | ||
| + | [[Category: Damberger FD]] | ||
Current revision
NMR solution structure of the N-terminal RRM and flanking linker regions of Polypyrimidine tract binding protein 1 using the CYANA CONSENSUS method.
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