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==AALALL SEGMENT FROM THE NUCLEOPROTEIN OF SARS-COV-2, RESIDUES 217-222, CRYSTAL FORM 1== | ==AALALL SEGMENT FROM THE NUCLEOPROTEIN OF SARS-COV-2, RESIDUES 217-222, CRYSTAL FORM 1== | ||
<StructureSection load='7ltu' size='340' side='right'caption='[[7ltu]]' scene=''> | <StructureSection load='7ltu' size='340' side='right'caption='[[7ltu]], [[Resolution|resolution]] 1.12Å' 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=7LTU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LTU FirstGlance]. <br> | <table><tr><td colspan='2'>[[7ltu]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7LTU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LTU FirstGlance]. <br> | ||
</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=7ltu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ltu OCA], [https://pdbe.org/7ltu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ltu RCSB], [https://www.ebi.ac.uk/pdbsum/7ltu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ltu ProSAT]</span></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=TFA:TRIFLUOROACETIC+ACID'>TFA</scene></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=7ltu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ltu OCA], [https://pdbe.org/7ltu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ltu RCSB], [https://www.ebi.ac.uk/pdbsum/7ltu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ltu ProSAT]</span></td></tr> | |||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The SARS-CoV-2 Nucleoprotein (NCAP) functions in RNA packaging during viral replication and assembly. Computational analysis of its amino acid sequence reveals a central low-complexity domain (LCD) having sequence features akin to LCDs in other proteins known to function in liquid-liquid phase separation. Here we show that in the presence of viral RNA, NCAP, and also its LCD segment alone, form amyloid-like fibrils when undergoing liquid-liquid phase separation. Within the LCD we identified three 6-residue segments that drive amyloid fibril formation. We determined atomic structures for fibrils formed by each of the three identified segments. These structures informed our design of peptide inhibitors of NCAP fibril formation and liquid-liquid phase separation, suggesting a therapeutic route for Covid-19. One Sentence Summary: Atomic structures of amyloid-driving peptide segments from SARS-CoV-2 Nucleoprotein inform the development of Covid-19 therapeutics. | |||
Inhibition of amyloid formation of the Nucleoprotein of SARS-CoV-2.,Tayeb-Fligelman E, Cheng X, Tai C, Bowler JT, Griner S, Sawaya MR, Seidler PM, Jiang YX, Lu J, Rosenberg GM, Salwinski L, Abskharon R, Zee CT, Hou K, Li Y, Boyer DR, Murray KA, Falcon G, Anderson DH, Cascio D, Saelices L, Damoiseaux R, Guo F, Eisenberg DS bioRxiv. 2021 Mar 5. doi: 10.1101/2021.03.05.434000. PMID:33688654<ref>PMID:33688654</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7ltu" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Eisenberg | [[Category: Eisenberg, D S]] | ||
[[Category: Rodriguez | [[Category: Rodriguez, J A]] | ||
[[Category: Sawaya | [[Category: Sawaya, M R]] | ||
[[Category: Zee C | [[Category: Zee, C T]] | ||
[[Category: Amyloid fibril]] | |||
[[Category: Protein fibril]] | |||
Revision as of 09:55, 24 March 2021
AALALL SEGMENT FROM THE NUCLEOPROTEIN OF SARS-COV-2, RESIDUES 217-222, CRYSTAL FORM 1AALALL SEGMENT FROM THE NUCLEOPROTEIN OF SARS-COV-2, RESIDUES 217-222, CRYSTAL FORM 1
Structural highlights
Publication Abstract from PubMedThe SARS-CoV-2 Nucleoprotein (NCAP) functions in RNA packaging during viral replication and assembly. Computational analysis of its amino acid sequence reveals a central low-complexity domain (LCD) having sequence features akin to LCDs in other proteins known to function in liquid-liquid phase separation. Here we show that in the presence of viral RNA, NCAP, and also its LCD segment alone, form amyloid-like fibrils when undergoing liquid-liquid phase separation. Within the LCD we identified three 6-residue segments that drive amyloid fibril formation. We determined atomic structures for fibrils formed by each of the three identified segments. These structures informed our design of peptide inhibitors of NCAP fibril formation and liquid-liquid phase separation, suggesting a therapeutic route for Covid-19. One Sentence Summary: Atomic structures of amyloid-driving peptide segments from SARS-CoV-2 Nucleoprotein inform the development of Covid-19 therapeutics. Inhibition of amyloid formation of the Nucleoprotein of SARS-CoV-2.,Tayeb-Fligelman E, Cheng X, Tai C, Bowler JT, Griner S, Sawaya MR, Seidler PM, Jiang YX, Lu J, Rosenberg GM, Salwinski L, Abskharon R, Zee CT, Hou K, Li Y, Boyer DR, Murray KA, Falcon G, Anderson DH, Cascio D, Saelices L, Damoiseaux R, Guo F, Eisenberg DS bioRxiv. 2021 Mar 5. doi: 10.1101/2021.03.05.434000. PMID:33688654[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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