3les

From Proteopedia

(Difference between revisions)

Current revision

2F5 Epitope scaffold ES2

Structural highlights

3les is a 2 chain structure with sequence from Thermus aquaticus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.77Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

SIGA_THEAQ Sigma factors are initiation factors that promote the attachment of RNA polymerase to specific initiation sites and are then released. This sigma factor is the primary sigma factor during exponential growth.[HAMAP-Rule:MF_00963]^[1] ^[2]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Elicitation of antibodies against targets that are immunorecessive, cryptic, or transient in their native context has been a challenge for vaccine design. Here we demonstrate the elicitation of structure-specific antibodies against the HIV-1 gp41 epitope of the broadly neutralizing antibody 2F5. This conformationally flexible region of gp41 assumes mostly helical conformations but adopts a kinked, extended structure when bound by antibody 2F5. Computational techniques were employed to transplant the 2F5 epitope into select acceptor scaffolds. The resultant "2F5-epitope scaffolds" possessed nanomolar affinity for antibody 2F5 and a range of epitope flexibilities and antigenic specificities. Crystallographic characterization of the epitope scaffold with highest affinity and antigenic discrimination confirmed good to near perfect attainment of the target conformation for the gp41 molecular graft in free and 2F5-bound states, respectively. Animals immunized with 2F5-epitope scaffolds showed levels of graft-specific immune responses that correlated with graft flexibility (p < 0.04), while antibody responses against the graft-as dissected residue-by-residue with alanine substitutions-resembled more closely those of 2F5 than sera elicited with flexible or cyclized peptides, a resemblance heightened by heterologous prime-boost. Lastly, crystal structures of a gp41 peptide in complex with monoclonal antibodies elicited by the 2F5-epitope scaffolds revealed that the elicited antibodies induce gp41 to assume its 2F5-recognized shape. Epitope scaffolds thus provide a means to elicit antibodies that recognize a predetermined target shape and sequence, even if that shape is transient in nature, and a means by which to dissect factors influencing such elicitation.

Elicitation of structure-specific antibodies by epitope scaffolds.,Ofek G, Guenaga FJ, Schief WR, Skinner J, Baker D, Wyatt R, Kwong PD Proc Natl Acad Sci U S A. 2010 Oct 19;107(42):17880-7. Epub 2010 Sep 27. PMID:20876137^[3]

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

References

↑ Minakhin L, Nechaev S, Campbell EA, Severinov K. Recombinant Thermus aquaticus RNA polymerase, a new tool for structure-based analysis of transcription. J Bacteriol. 2001 Jan;183(1):71-6. PMID:11114902 doi:http://dx.doi.org/10.1128/JB.183.1.71-76.2001
↑ Campbell EA, Muzzin O, Chlenov M, Sun JL, Olson CA, Weinman O, Trester-Zedlitz ML, Darst SA. Structure of the bacterial RNA polymerase promoter specificity sigma subunit. Mol Cell. 2002 Mar;9(3):527-39. PMID:11931761
↑ Ofek G, Guenaga FJ, Schief WR, Skinner J, Baker D, Wyatt R, Kwong PD. Elicitation of structure-specific antibodies by epitope scaffolds. Proc Natl Acad Sci U S A. 2010 Oct 19;107(42):17880-7. Epub 2010 Sep 27. PMID:20876137 doi:10.1073/pnas.1004728107

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3les"

@@ Line 1: / Line 1: @@
-{{STRUCTURE_3les|  PDB=3les  |  SCENE=  }}
-===2F5 Epitope scaffold ES2===
-{{ABSTRACT_PUBMED_20876137}}
-==Function==
+==2F5 Epitope scaffold ES2==
-[[http://www.uniprot.org/uniprot/Q9EZJ8_THEAQ Q9EZJ8_THEAQ]] Sigma factors are initiation factors that promote the attachment of RNA polymerase to specific initiation sites and are then released (By similarity).[RuleBase:RU000715]
+<StructureSection load='3les' size='340' side='right'caption='[[3les]], [[Resolution|resolution]] 2.77&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[3les]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Thermus_aquaticus Thermus aquaticus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3LES OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3LES 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]] 2.77&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=3les FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3les OCA], [https://pdbe.org/3les PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3les RCSB], [https://www.ebi.ac.uk/pdbsum/3les PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3les ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/SIGA_THEAQ SIGA_THEAQ] Sigma factors are initiation factors that promote the attachment of RNA polymerase to specific initiation sites and are then released. This sigma factor is the primary sigma factor during exponential growth.[HAMAP-Rule:MF_00963]<ref>PMID:11114902</ref> <ref>PMID:11931761</ref>
+== Evolutionary Conservation ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/le/3les_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3les ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Elicitation of antibodies against targets that are immunorecessive, cryptic, or transient in their native context has been a challenge for vaccine design. Here we demonstrate the elicitation of structure-specific antibodies against the HIV-1 gp41 epitope of the broadly neutralizing antibody 2F5. This conformationally flexible region of gp41 assumes mostly helical conformations but adopts a kinked, extended structure when bound by antibody 2F5. Computational techniques were employed to transplant the 2F5 epitope into select acceptor scaffolds. The resultant "2F5-epitope scaffolds" possessed nanomolar affinity for antibody 2F5 and a range of epitope flexibilities and antigenic specificities. Crystallographic characterization of the epitope scaffold with highest affinity and antigenic discrimination confirmed good to near perfect attainment of the target conformation for the gp41 molecular graft in free and 2F5-bound states, respectively. Animals immunized with 2F5-epitope scaffolds showed levels of graft-specific immune responses that correlated with graft flexibility (p &lt; 0.04), while antibody responses against the graft-as dissected residue-by-residue with alanine substitutions-resembled more closely those of 2F5 than sera elicited with flexible or cyclized peptides, a resemblance heightened by heterologous prime-boost. Lastly, crystal structures of a gp41 peptide in complex with monoclonal antibodies elicited by the 2F5-epitope scaffolds revealed that the elicited antibodies induce gp41 to assume its 2F5-recognized shape. Epitope scaffolds thus provide a means to elicit antibodies that recognize a predetermined target shape and sequence, even if that shape is transient in nature, and a means by which to dissect factors influencing such elicitation.
-==About this Structure==
+Elicitation of structure-specific antibodies by epitope scaffolds.,Ofek G, Guenaga FJ, Schief WR, Skinner J, Baker D, Wyatt R, Kwong PD Proc Natl Acad Sci U S A. 2010 Oct 19;107(42):17880-7. Epub 2010 Sep 27. PMID:20876137<ref>PMID:20876137</ref>
-[[3les]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Thermus_aquaticus Thermus aquaticus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3LES OCA].
-==Reference==
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-<ref group="xtra">PMID:020876137</ref><references group="xtra"/><references/>
+</div>
+<div class="pdbe-citations 3les" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Sigma factor 3D structures|Sigma factor 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
 [[Category: Thermus aquaticus]]
-[[Category: Baker, D.]]
+[[Category: Baker D]]
-[[Category: Guenaga, F J.]]
+[[Category: Guenaga FJ]]
-[[Category: Kwong, P D.]]
+[[Category: Kwong PD]]
-[[Category: Ofek, G.]]
+[[Category: Ofek G]]
-[[Category: Schief, W R.]]
+[[Category: Schief WR]]
-[[Category: Skinner, J.]]
+[[Category: Skinner J]]
-[[Category: Wyatt, R.]]
+[[Category: Wyatt R]]
-[[Category: 2f5]]
-[[Category: Epitope]]
-[[Category: Gp41]]
-[[Category: Graft]]
-[[Category: Hiv-1]]
-[[Category: Immune system]]
-[[Category: Monoclonal antibody]]
-[[Category: Re-elicitation]]
-[[Category: Scaffold]]
-[[Category: Sigma factor]]
-[[Category: Transplant]]
-[[Category: Vaccine design]]

3les

From Proteopedia

Current revision

2F5 Epitope scaffold ES2

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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