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6u54

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Revision as of 10:57, 4 December 2019

Anti-Zaire ebolavirus Nucleoprotein Single Domain Antibody Zaire C (ZC) Complexed with Zaire ebolavirus Nucleoprotein C-terminal Domain 634-739

Structural highlights

6u54 is a 2 chain structure with sequence from Camelus glama and Eboz5. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	NP (EBOZ5)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[NCAP_EBOZ5] Oligomerizes into helical capsid to encapsidate the viral genome, protecting it from nucleases and the cellular innate immune response. VP35 binds to and stabilizes monomeric NP, keeping it soluble. Upon virus replication, NP is recruited to bind cooperatively viral genomic RNA and VP35 is released. The encapsidated genomic RNA is termed the nucleocapsid and serves as template for transcription and replication. The nucleocapsid is helical with a pitch of 10.81 NP per turn and a diameter of about 22nm. Each NP binds to six nucleotides of viral genomic RNA, three being exposed to the solvant and three hidden into the nucleocapsid. Recruits also host PPP2R5C phosphatase to dephosphorylate VP30 and thereby promote viral transcription. Upon virion assembly and budding, NP binds to VP24 and possibly host STAU1.[UniProtKB:P18272]

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^[1]

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

References

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

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6u54"

@@ Line 3: / Line 3: @@
 <StructureSection load='6u54' size='340' side='right'caption='[[6u54]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6u54]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6U54 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6U54 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6u54]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Camelus_glama Camelus glama] and [http://en.wikipedia.org/wiki/Eboz5 Eboz5]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6U54 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6U54 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=6u54 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6u54 OCA], [http://pdbe.org/6u54 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6u54 RCSB], [http://www.ebi.ac.uk/pdbsum/6u54 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6u54 ProSAT]</span></td></tr>
+</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NP ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=128951 EBOZ5])</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=6u54 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6u54 OCA], [http://pdbe.org/6u54 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6u54 RCSB], [http://www.ebi.ac.uk/pdbsum/6u54 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6u54 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 17: / Line 18: @@
 </div>
 <div class="pdbe-citations 6u54" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Nucleoprotein 3D structures|Nucleoprotein 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Camelus glama]]
+[[Category: Eboz5]]
 [[Category: Large Structures]]
 [[Category: Hart, P J]]

6u54

From Proteopedia

Revision as of 10:57, 4 December 2019

Anti-Zaire ebolavirus Nucleoprotein Single Domain Antibody Zaire C (ZC) Complexed with Zaire ebolavirus Nucleoprotein C-terminal Domain 634-739

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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