7bx7: Difference between revisions
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==Cryo-EM structure of amyloid fibril formed by hnRNPA1 low complexity domain== | ==Cryo-EM structure of amyloid fibril formed by hnRNPA1 low complexity domain== | ||
<StructureSection load='7bx7' size='340' side='right'caption='[[7bx7]]' scene=''> | <StructureSection load='7bx7' size='340' side='right'caption='[[7bx7]], [[Resolution|resolution]] 2.80Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7BX7 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=7BX7 FirstGlance]. <br> | <table><tr><td colspan='2'>[[7bx7]] is a 6 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=7BX7 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=7BX7 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=7bx7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7bx7 OCA], [http://pdbe.org/7bx7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=7bx7 RCSB], [http://www.ebi.ac.uk/pdbsum/7bx7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=7bx7 ProSAT]</span></td></tr> | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HNRNPA1, HNRPA1 ([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://proteopedia.org/fgij/fg.htm?mol=7bx7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7bx7 OCA], [http://pdbe.org/7bx7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=7bx7 RCSB], [http://www.ebi.ac.uk/pdbsum/7bx7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=7bx7 ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Disease == | |||
[[http://www.uniprot.org/uniprot/ROA1_HUMAN ROA1_HUMAN]] Amyotrophic lateral sclerosis;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> The disease is caused by mutations affecting the gene represented in this entry.<ref>PMID:23455423</ref> | |||
== Function == | |||
[[http://www.uniprot.org/uniprot/ROA1_HUMAN ROA1_HUMAN]] Involved in the packaging of pre-mRNA into hnRNP particles, transport of poly(A) mRNA from the nucleus to the cytoplasm and may modulate splice site selection. May play a role in HCV RNA replication.<ref>PMID:17229681</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Human heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) serves as a key regulating protein in RNA metabolism. Malfunction of hnRNPA1 in nucleo-cytoplasmic transport or dynamic phase separation leads to abnormal amyloid aggregation and neurodegeneration. The low complexity (LC) domain of hnRNPA1 drives both dynamic phase separation and amyloid aggregation. Here, we use cryo-electron microscopy to determine the amyloid fibril structure formed by hnRNPA1 LC domain. Remarkably, the structure reveals that the nuclear localization sequence of hnRNPA1 (termed PY-NLS), which is initially known to mediate the nucleo-cytoplamic transport of hnRNPA1 through binding with karyopherin-beta2 (Kapbeta2), represents the major component of the fibril core. The residues that contribute to the binding of PY-NLS with Kapbeta2 also exert key molecular interactions to stabilize the fibril structure. Notably, hnRNPA1 mutations found in familial amyotrophic lateral sclerosis (ALS) and multisystem proteinopathoy (MSP) are all involved in the fibril core and contribute to fibril stability. Our work illuminates structural understandings of the pathological amyloid aggregation of hnRNPA1 and the amyloid disaggregase activity of Kapbeta2, and highlights the multiple roles of PY-NLS in hnRNPA1 homeostasis. | |||
The nuclear localization sequence mediates hnRNPA1 amyloid fibril formation revealed by cryoEM structure.,Sun Y, Zhao K, Xia W, Feng G, Gu J, Ma Y, Gui X, Zhang X, Fang Y, Sun B, Wang R, Liu C, Li D Nat Commun. 2020 Dec 11;11(1):6349. doi: 10.1038/s41467-020-20227-8. PMID:33311513<ref>PMID:33311513</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7bx7" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Human]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Li D]] | [[Category: Li, D]] | ||
[[Category: Liu C]] | [[Category: Liu, C]] | ||
[[Category: Sun | [[Category: Sun, Y P]] | ||
[[Category: Zhao K]] | [[Category: Zhao, K]] | ||
[[Category: Amyloid fibril]] | |||
[[Category: Protein fibril]] | |||