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3lrh

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Structure of anti-huntingtin VL domain in complex with huntingtin peptide

Structural highlights

3lrh is a 16 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.6Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

HD_HUMAN Juvenile Huntington disease;Huntington disease. The disease is caused by mutations affecting the gene represented in this entry.

Function

HD_HUMAN May play a role in microtubule-mediated transport or vesicle function.

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 Disease
3 Function
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

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

Categories: Homo sapiens | Large Structures | Chatwell L | Schiefner A | Skerra A

@@ Line 3: / Line 3: @@
 <StructureSection load='3lrh' size='340' side='right'caption='[[3lrh]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3lrh]] is a 16 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3LRH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3LRH FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3lrh]] is a 16 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3LRH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3LRH FirstGlance]. <br>
-</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3lrg|3lrg]]</div></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.6&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">VL12.3 ([https://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'>[https://proteopedia.org/fgij/fg.htm?mol=3lrh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3lrh OCA], [https://pdbe.org/3lrh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3lrh RCSB], [https://www.ebi.ac.uk/pdbsum/3lrh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3lrh ProSAT]</span></td></tr>
 </table>
 == Disease ==
-[[https://www.uniprot.org/uniprot/HD_HUMAN HD_HUMAN]] Juvenile Huntington disease;Huntington disease. The disease is caused by mutations affecting the gene represented in this entry.
+[https://www.uniprot.org/uniprot/HD_HUMAN HD_HUMAN] Juvenile Huntington disease;Huntington disease. The disease is caused by mutations affecting the gene represented in this entry.
 == Function ==
-[[https://www.uniprot.org/uniprot/HD_HUMAN HD_HUMAN]] May play a role in microtubule-mediated transport or vesicle function.
+[https://www.uniprot.org/uniprot/HD_HUMAN HD_HUMAN] May play a role in microtubule-mediated transport or vesicle function.
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 25: / Line 24: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Chatwell, L]]
+[[Category: Chatwell L]]
-[[Category: Schiefner, A]]
+[[Category: Schiefner A]]
-[[Category: Skerra, A]]
+[[Category: Skerra A]]
-[[Category: Huntingtin]]
-[[Category: Huntington's disease]]
-[[Category: Immune system]]
-[[Category: Immunoglobulin]]
-[[Category: Intrabody]]
-[[Category: Variable light chain domain]]

3lrh

From Proteopedia

Current revision

Structure of anti-huntingtin VL domain in complex with huntingtin peptide

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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