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| | <StructureSection load='6wpq' size='340' side='right'caption='[[6wpq]], [[Resolution|resolution]] 1.10Å' scene=''> | | <StructureSection load='6wpq' size='340' side='right'caption='[[6wpq]], [[Resolution|resolution]] 1.10Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6wpq]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6WPQ OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6WPQ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6wpq]] is a 1 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=6WPQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6WPQ FirstGlance]. <br> |
| - | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6wpq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6wpq OCA], [http://pdbe.org/6wpq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6wpq RCSB], [http://www.ebi.ac.uk/pdbsum/6wpq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6wpq ProSAT]</span></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]] 1.1Å</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=6wpq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6wpq OCA], [https://pdbe.org/6wpq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6wpq RCSB], [https://www.ebi.ac.uk/pdbsum/6wpq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6wpq ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/ROA2_HUMAN ROA2_HUMAN]] Inclusion body myopathy with Paget disease of bone and frontotemporal dementia. The disease is caused by mutations affecting the gene represented in this entry.<ref>PMID:23455423</ref> | + | [https://www.uniprot.org/uniprot/ROA2_HUMAN ROA2_HUMAN] Inclusion body myopathy with Paget disease of bone and frontotemporal dementia. The disease is caused by mutations affecting the gene represented in this entry.<ref>PMID:23455423</ref> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/ROA2_HUMAN ROA2_HUMAN]] Involved with pre-mRNA processing. Forms complexes (ribonucleosomes) with at least 20 other different hnRNP and heterogeneous nuclear RNA in the nucleus. | + | [https://www.uniprot.org/uniprot/ROA2_HUMAN ROA2_HUMAN] Involved with pre-mRNA processing. Forms complexes (ribonucleosomes) with at least 20 other different hnRNP and heterogeneous nuclear RNA in the nucleus. |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | hnRNPA2 is a human ribonucleoprotein (RNP) involved in RNA metabolism. It forms fibrils both under cellular stress and in mutated form in neurodegenerative conditions. Previous work established that the C-terminal low-complexity domain (LCD) of hnRNPA2 fibrillizes under stress, and missense mutations in this domain are found in the disease multisystem proteinopathy (MSP). However, little is known at the atomic level about the hnRNPA2 LCD structure that is involved in those processes and how disease mutations cause structural change. Here we present the cryo-electron microscopy (cryoEM) structure of the hnRNPA2 LCD fibril core and demonstrate its capability to form a reversible hydrogel in vitro containing amyloid-like fibrils. Whereas these fibrils, like pathogenic amyloid, are formed from protein chains stacked into beta-sheets by backbone hydrogen bonds, they display distinct structural differences: the chains are kinked, enabling non-covalent cross-linking of fibrils and disfavoring formation of pathogenic steric zippers. Both reversibility and energetic calculations suggest these fibrils are less stable than pathogenic amyloid. Moreover, the crystal structure of the disease-mutation-containing segment (D290V) of hnRNPA2 suggests that the replacement fundamentally alters the fibril structure to a more stable energetic state. These findings illuminate how molecular interactions promote protein fibril networks and how mutation can transform fibril structure from functional to a pathogenic form.
| + | |
| - | | + | |
| - | CryoEM structure of the low-complexity domain of hnRNPA2 and its conversion to pathogenic amyloid.,Lu J, Cao Q, Hughes MP, Sawaya MR, Boyer DR, Cascio D, Eisenberg DS Nat Commun. 2020 Aug 14;11(1):4090. doi: 10.1038/s41467-020-17905-y. PMID:32796831<ref>PMID:32796831</ref>
| + | |
| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 6wpq" style="background-color:#fffaf0;"></div>
| + | |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Boyer, D R]] | + | [[Category: Boyer DR]] |
| - | [[Category: Cao, Q]] | + | [[Category: Cao Q]] |
| - | [[Category: Cascio, D]] | + | [[Category: Cascio D]] |
| - | [[Category: Eisenberg, D S]] | + | [[Category: Eisenberg DS]] |
| - | [[Category: Hughes, M P]] | + | [[Category: Hughes MP]] |
| - | [[Category: Lu, J]] | + | [[Category: Lu J]] |
| - | [[Category: Sawaya, M R]] | + | [[Category: Sawaya MR]] |
| - | [[Category: Amyloid-like fibril]]
| + | |
| - | [[Category: Amyloidogenic segment]]
| + | |
| - | [[Category: Disease related]]
| + | |
| - | [[Category: Protein fibril]]
| + | |
| Structural highlights
Disease
ROA2_HUMAN Inclusion body myopathy with Paget disease of bone and frontotemporal dementia. The disease is caused by mutations affecting the gene represented in this entry.[1]
Function
ROA2_HUMAN Involved with pre-mRNA processing. Forms complexes (ribonucleosomes) with at least 20 other different hnRNP and heterogeneous nuclear RNA in the nucleus.
References
- ↑ Kim HJ, Kim NC, Wang YD, Scarborough EA, Moore J, Diaz Z, MacLea KS, Freibaum B, Li S, Molliex A, Kanagaraj AP, Carter R, Boylan KB, Wojtas AM, Rademakers R, Pinkus JL, Greenberg SA, Trojanowski JQ, Traynor BJ, Smith BN, Topp S, Gkazi AS, Miller J, Shaw CE, Kottlors M, Kirschner J, Pestronk A, Li YR, Ford AF, Gitler AD, Benatar M, King OD, Kimonis VE, Ross ED, Weihl CC, Shorter J, Taylor JP. Mutations in prion-like domains in hnRNPA2B1 and hnRNPA1 cause multisystem proteinopathy and ALS. Nature. 2013 Mar 28;495(7442):467-73. doi: 10.1038/nature11922. Epub 2013 Mar 3. PMID:23455423 doi:http://dx.doi.org/10.1038/nature11922
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