5y4m
From Proteopedia
(Difference between revisions)
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<StructureSection load='5y4m' size='340' side='right' caption='[[5y4m]], [[Resolution|resolution]] 1.31Å' scene=''> | <StructureSection load='5y4m' size='340' side='right' caption='[[5y4m]], [[Resolution|resolution]] 1.31Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[5y4m]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5Y4M OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5Y4M FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5y4m]] is a 1 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=5Y4M OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5Y4M FirstGlance]. <br> |
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CNTNAP2, CASPR2, KIAA0868 ([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=5y4m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5y4m OCA], [http://pdbe.org/5y4m PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5y4m RCSB], [http://www.ebi.ac.uk/pdbsum/5y4m PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5y4m ProSAT]</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=5y4m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5y4m OCA], [http://pdbe.org/5y4m PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5y4m RCSB], [http://www.ebi.ac.uk/pdbsum/5y4m PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5y4m ProSAT]</span></td></tr> | ||
</table> | </table> | ||
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== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/CNTP2_HUMAN CNTP2_HUMAN]] Required, with CNTNAP1, for radial and longitudinal organization of myelinated axons. Plays a role in the formation of functional distinct domains critical for saltatory conduction of nerve impulses in myelinated nerve fibers. Demarcates the juxtaparanodal region of the axo-glial junction.[UniProtKB:Q9CPW0] | [[http://www.uniprot.org/uniprot/CNTP2_HUMAN CNTP2_HUMAN]] Required, with CNTNAP1, for radial and longitudinal organization of myelinated axons. Plays a role in the formation of functional distinct domains critical for saltatory conduction of nerve impulses in myelinated nerve fibers. Demarcates the juxtaparanodal region of the axo-glial junction.[UniProtKB:Q9CPW0] | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Accumulating evidence has showed that anti-CASPR2 autoantibodies occur in a long list of neurological immune disorders including limbic encephalitis (LE). Belonging to the well-known neurexin superfamily, CASPR2 has been suggested to be a central node in the molecular networks controlling neurodevelopment. Distinct from other subfamilies in the neurexin superfamily, the CASPR subfamily features a unique discoidin (Disc) domain. As revealed by our and others' recent studies, CASPR2 Disc domain bears a major epitope for autoantibodies. However, structural information on CASPR2 recognition by autoantibodies has been lacking. Here, we report the crystal structure of human CASPR2 Disc domain at a high resolution of 1.31A, which is the first atomic-resolution structure of the CASPR subfamily members. The Disc domain adopts a total beta structure and folds into a distorted jellyroll-like barrel with a conserved disulfide-bond interlocking its N- and C-termini. Defined by four loops and located in one end of the barrel, the "loop-tip surface" is totally polar and easily available for protein docking. Based on structure-guided epitope prediction, we generated nine mutants and evaluated their binding to autoantibodies of cerebrospinal fluid from twelve patients with limbic encephalitis. The quadruple mutant G69N/A71S/S77N/D78R impaired CASPR2 binding to autoantibodies from eleven LE patients, which indicates that the loop L1 in the Disc domain bears hot spots for autoantibody interaction. Structural mapping of autoepitopes within human CASPR2 Disc domain sheds light on how autoantibodies could sequester CASPR2 ectodomain and antagonize its functionalities in the pathogenic processes. | ||
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| + | Structural mapping of hot spots within human CASPR2 discoidin domain for autoantibody recognition.,Liang W, Zhang J, Saint-Martin M, Xu F, Noraz N, Liu J, Honnorat J, Liu H J Autoimmun. 2019 Jan;96:168-177. doi: 10.1016/j.jaut.2018.09.012. Epub 2018 Oct , 15. PMID:30337146<ref>PMID:30337146</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 5y4m" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Human]] | ||
[[Category: Liang, W]] | [[Category: Liang, W]] | ||
[[Category: Liu, H]] | [[Category: Liu, H]] | ||
Revision as of 07:39, 21 February 2019
Discoidin domain of human CASPR2
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Categories: Human | Liang, W | Liu, H | Xu, F | Zhang, J | Cell adhesion | Epitope for autoantibody
