5hbt

From Proteopedia

(Difference between revisions)

Current revision

Complex structure of Fab35 and human nAChR alpha1

Structural highlights

5hbt is a 4 chain structure with sequence from Bungarus multicinctus, Homo sapiens and Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.61Å
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 nicotinic acetylcholine receptor (nAChR) is a major target of autoantibodies in myasthenia gravis (MG), an autoimmune disease that causes neuromuscular transmission dysfunction. Despite decades of research, the molecular mechanisms underlying MG have not been fully elucidated. Here, we present the crystal structure of the nAChR alpha1 subunit bound by the Fab fragment of mAb35, a reference monoclonal antibody that causes experimental MG and competes with ~65% of antibodies from MG patients. Our structures reveal for the first time the detailed molecular interactions between MG antibodies and a core region on nAChR alpha1. These structures suggest a major nAChR-binding mechanism shared by a large number of MG antibodies and the possibility to treat MG by blocking this binding mechanism. Structure-based modeling also provides insights into antibody-mediated nAChR cross-linking known to cause receptor degradation. Our studies establish a structural basis for further mechanistic studies and therapeutic development of MG.

Structural insights into the molecular mechanisms of myasthenia gravis and their therapeutic implications.,Noridomi K, Watanabe G, Hansen MN, Han GW, Chen L Elife. 2017 Apr 25;6. pii: e23043. doi: 10.7554/eLife.23043. PMID:28440223^[1]

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

References

↑ Noridomi K, Watanabe G, Hansen MN, Han GW, Chen L. Structural insights into the molecular mechanisms of myasthenia gravis and their therapeutic implications. Elife. 2017 Apr 25;6. pii: e23043. doi: 10.7554/eLife.23043. PMID:28440223 doi:http://dx.doi.org/10.7554/eLife.23043

1 Structural highlights
2 Disease
3 Function
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/5hbt"

@@ Line 3: / Line 3: @@
 <StructureSection load='5hbt' size='340' side='right'caption='[[5hbt]], [[Resolution|resolution]] 2.61&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5hbt]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Bungarus_multicinctus Bungarus multicinctus], [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5HBT OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5HBT FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5hbt]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Bungarus_multicinctus Bungarus multicinctus], [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5HBT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5HBT FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></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]] 2.61&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5hbv|5hbv]]</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CHRNA1, hCG_1811440 ([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'>[https://proteopedia.org/fgij/fg.htm?mol=5hbt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hbt OCA], [https://pdbe.org/5hbt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5hbt RCSB], [https://www.ebi.ac.uk/pdbsum/5hbt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5hbt ProSAT]</span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5hbt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hbt OCA], [http://pdbe.org/5hbt PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5hbt RCSB], [http://www.ebi.ac.uk/pdbsum/5hbt PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5hbt ProSAT]</span></td></tr>
 </table>
+== Disease ==
+[https://www.uniprot.org/uniprot/ACHA_HUMAN 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 ==
-[[http://www.uniprot.org/uniprot/3L21V_BUNMU 3L21V_BUNMU]] Binds with high affinity to muscular (alpha-1/CHRNA1) and neuronal (alpha-7/CHRNA7) nicotinic acetylcholine receptor (nAChR) and inhibits acetylcholine from binding to the receptor, thereby impairing neuromuscular and neuronal transmission.[UniProtKB:P60615]<ref>PMID:10497260</ref>
+[https://www.uniprot.org/uniprot/ACHA_HUMAN 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.
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 22: / Line 23: @@
 ==See Also==
+*[[Acetyl choline receptor 3D structures|Acetyl choline receptor 3D structures]]
 *[[Bungarotoxin 3D structures|Bungarotoxin 3D structures]]
-*[[Nicotinic Acetylcholine Receptor|Nicotinic Acetylcholine Receptor]]
 == References ==
 <references/>
@@ Line 29: / Line 30: @@
 </StructureSection>
 [[Category: Bungarus multicinctus]]
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
 [[Category: Rattus norvegicus]]
-[[Category: Chen, L]]
+[[Category: Chen L]]
-[[Category: Han, G W]]
+[[Category: Han GW]]
-[[Category: Hansen, M N]]
+[[Category: Hansen MN]]
-[[Category: Noridomi, K]]
+[[Category: Noridomi K]]
-[[Category: Watanabe, G]]
+[[Category: Watanabe G]]
-[[Category: Complex]]
-[[Category: Fab35]]
-[[Category: Myasthenia gravi]]
-[[Category: Nicotinic acetylcholine receptor alpha1]]
-[[Category: Transport protein-toxin complex]]

5hbt

From Proteopedia

Current revision

Complex structure of Fab35 and human nAChR alpha1

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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