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4zjs

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Revision as of 09:53, 10 March 2017

Crystal structure of a chimeric acetylcholine binding protein from Aplysia Californica (Ac-AChBP) containing the main immunogenic region (MIR) from the human alpha 1 subunit of the muscle nicotinic acetylcholine receptor in complex with anatoxin-A.

Structural highlights

4zjs is a 5 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[ACHA_HUMAN] Postsynaptic congenital myasthenic syndromes;Lethal multiple pterygium syndrome. The disease is caused by mutations affecting the gene represented in this entry. The alpha subunit is the main focus for antibody binding in myasthenia gravis. Myasthenia gravis is characterized by sporadic muscular fatigability and weakness, occurring chiefly in muscles innervated by cranial nerves, and characteristically improved by cholinesterase-inhibiting drugs. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry.

Function

[ACHA_HUMAN] After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane.

Publication Abstract from PubMed

The main immunogenic region (MIR) is a conformation-dependent region at the extracellular apex of alpha1 subunits of muscle nicotinic acetylcholine receptor (AChR) that is the target of half or more of the autoantibodies to muscle AChRs in human myasthenia gravis and rat experimental autoimmune myasthenia gravis. By making chimeras of human alpha1 subunits with alpha7 subunits, both MIR epitopes recognized by rat mAbs and by the patient-derived human mAb 637 to the MIR were determined to consist of two discontiguous sequences, which are adjacent only in the native conformation. The MIR, including loop alpha1 67-76 in combination with the N-terminal alpha helix alpha1 1-14, conferred high-affinity binding for most rat mAbs to the MIR. However, an additional sequence corresponding to alpha1 15-32 was required for high-affinity binding of human mAb 637. A water soluble chimera of Aplysia acetylcholine binding protein with the same alpha1 MIR sequences substituted was recognized by a majority of human, feline, and canine myasthenia gravis sera. The presence of the alpha1 MIR sequences in alpha1/alpha7 chimeras greatly promoted AChR expression and significantly altered the sensitivity to activation. This reveals a structural and functional, as well as antigenic, significance of the MIR.

Main immunogenic region structure promotes binding of conformation-dependent myasthenia gravis autoantibodies, nicotinic acetylcholine receptor conformation maturation, and agonist sensitivity.,Luo J, Taylor P, Losen M, de Baets MH, Shelton GD, Lindstrom J J Neurosci. 2009 Nov 4;29(44):13898-908. doi: 10.1523/JNEUROSCI.2833-09.2009. PMID:19890000^[1]

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

References

↑ Luo J, Taylor P, Losen M, de Baets MH, Shelton GD, Lindstrom J. Main immunogenic region structure promotes binding of conformation-dependent myasthenia gravis autoantibodies, nicotinic acetylcholine receptor conformation maturation, and agonist sensitivity. J Neurosci. 2009 Nov 4;29(44):13898-908. doi: 10.1523/JNEUROSCI.2833-09.2009. PMID:19890000 doi:http://dx.doi.org/10.1523/JNEUROSCI.2833-09.2009

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/4zjs"

@@ Line 1: / Line 1: @@
 ==Crystal structure of a chimeric acetylcholine binding protein from Aplysia Californica (Ac-AChBP) containing the main immunogenic region (MIR) from the human alpha 1 subunit of the muscle nicotinic acetylcholine receptor in complex with anatoxin-A.==
 <StructureSection load='4zjs' size='340' side='right' caption='[[4zjs]], [[Resolution|resolution]] 2.23&Aring;' scene=''>
@@ Line 4: / Line 5: @@
 <table><tr><td colspan='2'>[[4zjs]] is a 5 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ZJS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ZJS FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4P0:1-[(1R,6R)-9-AZABICYCLO[4.2.1]NON-2-EN-2-YL]ETHANONE'>4P0</scene></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=4zjs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zjs OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4zjs RCSB], [http://www.ebi.ac.uk/pdbsum/4zjs 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=4zjs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zjs OCA], [http://pdbe.org/4zjs PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4zjs RCSB], [http://www.ebi.ac.uk/pdbsum/4zjs PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4zjs ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 18: / Line 19: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4zjs" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

4zjs

From Proteopedia

Revision as of 09:53, 10 March 2017

Crystal structure of a chimeric acetylcholine binding protein from Aplysia Californica (Ac-AChBP) containing the main immunogenic region (MIR) from the human alpha 1 subunit of the muscle nicotinic acetylcholine receptor in complex with anatoxin-A.

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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