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3lrg

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Revision as of 18:58, 5 August 2016

Structure of anti-huntingtin VL domain

Structural highlights

3lrg is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	3lrh
Gene:	VL12.3 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Publication Abstract from PubMed

We present the crystal structure and biophysical characterization of a human V(L) [variable domain immunoglobulin (Ig) light chain] single-domain intrabody that binds to the huntingtin (Htt) protein and has been engineered for antigen recognition in the absence of its intradomain disulfide bond, otherwise conserved in the Ig fold. Analytical ultracentrifugation demonstrated that the alphaHtt-V(L) 12.3 domain is a stable monomer under physiological conditions even at concentrations >20 muM. Using peptide SPOT arrays, we identified the minimal binding epitope to be EKLMKAFESLKSFQ, comprising the N-terminal residues 5-18 of Htt and including the first residue of the poly-Gln stretch. X-ray structural analysis of alphaHtt-V(L) both as apo protein and in the presence of the epitope peptide revealed several interesting insights: first, the role of mutations acquired during the combinatorial selection process of the alphaHtt-V(L) 12.3 domain-initially starting from a single-chain Fv fragment-that are responsible for its stability as an individually soluble Ig domain, also lacking the disulfide bridge, and second, a previously unknown mode of antigen recognition, revealing a novel paratope. The Htt epitope peptide adopts a purely alpha-helical structure in the complex with alphaHtt-V(L) and is bound at the base of the complementarity-determining regions (CDRs) at the concave beta-sheet that normally gives rise to the interface between the V(L) domain and its paired V(H) (variable domain Ig heavy chain) domain, while only few interactions with CDR-L1 and CDR-L3 are formed. Notably, this noncanonical mode of antigen binding may occur more widely in the area of in vitro selected antibody fragments, including other Ig-like scaffolds, possibly even if a V(H) domain is present.

A Disulfide-Free Single-Domain V(L) Intrabody with Blocking Activity towards Huntingtin Reveals a Novel Mode of Epitope Recognition.,Schiefner A, Chatwell L, Korner J, Neumaier I, Colby DW, Volkmer R, Wittrup KD, Skerra A J Mol Biol. 2011 Sep 24. PMID:21968397^[1]

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

References

↑ Schiefner A, Chatwell L, Korner J, Neumaier I, Colby DW, Volkmer R, Wittrup KD, Skerra A. A Disulfide-Free Single-Domain V(L) Intrabody with Blocking Activity towards Huntingtin Reveals a Novel Mode of Epitope Recognition. J Mol Biol. 2011 Sep 24. PMID:21968397 doi:10.1016/j.jmb.2011.09.034

1 Structural highlights
2 Publication Abstract from PubMed
3 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

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

@@ Line 1: / Line 1: @@
 ==Structure of anti-huntingtin VL domain==
 <StructureSection load='3lrg' size='340' side='right' caption='[[3lrg]], [[Resolution|resolution]] 2.05&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3lrg]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3LRG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3LRG FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3lrg]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3LRG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3LRG FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=IMD:IMIDAZOLE'>IMD</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3lrh|3lrh]]</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">VL12.3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">VL12.3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=3lrg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3lrg OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3lrg RCSB], [http://www.ebi.ac.uk/pdbsum/3lrg PDBsum]</span></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=3lrg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3lrg OCA], [http://pdbe.org/3lrg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3lrg RCSB], [http://www.ebi.ac.uk/pdbsum/3lrg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3lrg ProSAT]</span></td></tr>
 </table>
 <div style="background-color:#fffaf0;">
@@ Line 16: / Line 17: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 3lrg" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Homo sapiens]]
+[[Category: Human]]
 [[Category: Chatwell, L]]
 [[Category: Schiefner, A]]

3lrg

From Proteopedia

Revision as of 18:58, 5 August 2016

Structure of anti-huntingtin VL domain

Structural highlights

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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