View source for 6u50


==Anti-Sudan ebolavirus Nucleoprotein Single Domain Antibody Sudan B (SB)==
<StructureSection load='6u50' size='340' side='right'caption='[[6u50]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6u50]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Lama_glama Lama glama]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6U50 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6U50 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]] 1.6&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</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=6u50 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6u50 OCA], [https://pdbe.org/6u50 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6u50 RCSB], [https://www.ebi.ac.uk/pdbsum/6u50 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6u50 ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
We had previously shown that three anti-Marburgvirus nanobodies (VHH or sdAb) targeted a cryptotope within an alpha-helical assembly at the nucleoprotein (NP) C-terminus that was conserved through half a century of viral evolution. Here, we wished to determine whether an anti-Ebola virus sdAb, that was cross-reactive within the Ebolavirus genus, recognized a similar structural feature upstream of the ebolaviral NP C-terminus. Additionally, we sought to determine whether the specificities of a less cross-reactive anti-Zaire ebolavirus sdAb and a totally specific anti-Sudan ebolavirus sdAb were the result of exclusion from this region. Binding and X-ray crystallographic studies revealed that the primary determinant of cross-reactivity did indeed appear to be a preference for the helical feature. Specificity, in the case of the Zaire ebolavirus specific sdAb arose from the footprint shifting away from the helices, to engage more variable residues. While both sdAb employed CDRs they also had atypical side-on approaches with framework 2 (FR2) helping to accommodate parts of the epitope in sizeable paratope gullies. The Sudan ebolavirus specific sdAb was more remarkable and appeared to bind two C-terminal domains simultaneously via non-overlapping epitopes - "paratope duality". One mode involved paratope gullying, while the other involved only CDRs, with CDR3 restructuring to wedge in between opposing walls of an inter-domain crevice. The varied routes used by sdAb to engage antigen discovered here deepen our appreciation of the small scaffold's architectural versatility, and also reveal lucrative opportunities within the ebolavirus NP C-termini that might be leveraged for diagnostics and novel therapeutic targeting.

Paratope duality and gullying are among the atypical recognition mechanisms employed by a trio of nanobodies to differentiate ebolavirus nucleoproteins.,Sherwood LJ, Taylor AB, Hart PJ, Hayhurst A J Mol Biol. 2019 Oct 15. pii: S0022-2836(19)30597-2. doi:, 10.1016/j.jmb.2019.10.005. PMID:31626803<ref>PMID:31626803</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6u50" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Lama glama]]
[[Category: Large Structures]]
[[Category: Hart PJ]]
[[Category: Hayhurst A]]
[[Category: Sherwood LJ]]
[[Category: Taylor AB]]