6u8d: Difference between revisions
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==Crystal structure of hepatitis C virus IRES junction IIIabc in complex with Fab HCV2== | |||
<StructureSection load='6u8d' size='340' side='right'caption='[[6u8d]], [[Resolution|resolution]] 1.81Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6u8d]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6U8D OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6U8D FirstGlance]. <br> | |||
</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=6u8d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6u8d OCA], [http://pdbe.org/6u8d PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6u8d RCSB], [http://www.ebi.ac.uk/pdbsum/6u8d PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6u8d ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Structured RNA elements within the internal ribosome entry site (IRES) of hepatitis C virus (HCV) genome hijack host cell machinery for translation initiation through a cap-independent mechanism. Here, using a phage display selection, we obtained two antibody fragments (Fabs), HCV2 and HCV3, against HCV IRES that bind the RNA with dissociation constants of 32 +/- 7 nM and 37 +/- 8 nM respectively, specifically recognizing the so-called junction IIIabc (JIIIabc). We used these Fabs as crystallization chaperones and determined the high-resolution crystal structures of JIIIabc - HCV2 and - HCV3 complexes at 1.81-A and 2.75-A resolution respectively, revealing an anti-parallel four-way junction with the so-called IIIa and IIIc sub-domains brought together through tertiary interactions. The RNA conformation observed in the structures supports the structural model for this region derived from cryo-EM data for the HCV IRES - 40S ribosome complex, suggesting that the tertiary fold of the RNA pre-organizes the domain for interactions with the 40S ribosome. Strikingly, both Fabs and the ribosomal protein eS27 not only interact with a common subset of nucleotides within the JIIIabc but also use physio-chemically similar sets of protein residues to do so, suggesting that the RNA surface is well-suited for interactions with proteins, perhaps analogous to the 'hot spot' concept elaborated for protein-protein interactions. Using a rabbit reticulocyte lysate-based translation assay with a bicistronic reporter construct, we further demonstrated that Fabs HCV2 and HCV3 specifically inhibit the HCV IRES-directed translation, implicating disruption of the JIIIabc - ribosome interaction as a potential therapeutic strategy against HCV. | |||
Synthetic antibody binding to a pre-organized IRES RNA domain of hepatitis C virus inhibits translation.,Koirala D, Lewicka A, Koldobskaya Y, Huang H, Piccirilli JA ACS Chem Biol. 2019 Nov 25. doi: 10.1021/acschembio.9b00785. PMID:31765566<ref>PMID:31765566</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 6u8d" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Huang, H]] | |||
[[Category: Koirala, D]] | |||
[[Category: Koldobskaya, Y]] | |||
[[Category: Lewicka, A]] | |||
[[Category: Piccirilli, J A]] | |||
[[Category: Antibody-assisted rna crystallography]] | |||
[[Category: Hepatitis c virus]] | |||
[[Category: Junction iiiabc]] | |||
[[Category: Rna]] | |||
[[Category: Rna-immune system complex]] | |||
[[Category: Viral rna domain]] | |||
[[Category: Viral translation]] | |||
