6u8d: Difference between revisions

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~~'''Unreleased structure'''~~

~~The entry~~ 6u8d is ~~ON HOLD until Paper~~ Publication

==Crystal structure of hepatitis C virus IRES junction IIIabc in complex with Fab HCV2==

== Structural highlights ==

<table><tr><td colspan='2'>[[6u8d]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Hepacivirus_hominis Hepacivirus hominis] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. 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 [https://proteopedia.org/fgij/fg.htm?mol=6U8D FirstGlance]. <br>

</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.807Å</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=6u8d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6u8d OCA], [https://pdbe.org/6u8d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6u8d RCSB], [https://www.ebi.ac.uk/pdbsum/6u8d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6u8d ProSAT]</span></td></tr>

</table>

== 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.

~~Authors~~:

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>

~~Description~~:

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>

[[Category: ~~Unreleased~~ Structures]]

</div>

==See Also==

*[[Antibody 3D structures|Antibody 3D structures]]

== References ==

__TOC__

</StructureSection>

[[Category: Hepacivirus hominis]]

[[Category: Homo sapiens]]

[[Category: Large Structures]]

[[Category: Huang H]]

[[Category: Koirala D]]

[[Category: Koldobskaya Y]]

[[Category: Lewicka A]]

[[Category: Piccirilli JA]]

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@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 6u8d is ON HOLD  until Paper Publication
+==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]] 1.81&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[6u8d]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Hepacivirus_hominis Hepacivirus hominis] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. 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 [https://proteopedia.org/fgij/fg.htm?mol=6U8D FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.807&#8491;</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=6u8d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6u8d OCA], [https://pdbe.org/6u8d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6u8d RCSB], [https://www.ebi.ac.uk/pdbsum/6u8d PDBsum], [https://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.
-Authors:
+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>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 6u8d" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Antibody 3D structures|Antibody 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Hepacivirus hominis]]
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Huang H]]
+[[Category: Koirala D]]
+[[Category: Koldobskaya Y]]
+[[Category: Lewicka A]]
+[[Category: Piccirilli JA]]