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5hbv

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Revision as of 06:58, 20 May 2020

Complex structure of Fab35 and mouse nAChR alpha1

Structural highlights

5hbv is a 4 chain structure with sequence from Bungarus multicinctus, Lk3 transgenic mice and Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Related:	5hbt
Gene:	Chrna1, Acra (LK3 transgenic mice)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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]^[1] [ACHA_MOUSE] 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^[2]

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

References

↑ Chang L, Lin S, Huang H, Hsiao M. Genetic organization of alpha-bungarotoxins from Bungarus multicinctus (Taiwan banded krait): evidence showing that the production of alpha-bungarotoxin isotoxins is not derived from edited mRNAs. Nucleic Acids Res. 1999 Oct 15;27(20):3970-5. PMID:10497260
↑ 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 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5hbv"

@@ Line 1: / Line 1: @@
 ==Complex structure of Fab35 and mouse nAChR alpha1==
-<StructureSection load='5hbv' size='340' side='right' caption='[[5hbv]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
+<StructureSection load='5hbv' size='340' side='right'caption='[[5hbv]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5hbv]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/ ], [http://en.wikipedia.org/wiki/Bungarus_multicinctus Bungarus multicinctus] 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=5HBV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5HBV FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5hbv]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Bungarus_multicinctus Bungarus multicinctus], [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice] 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=5HBV OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5HBV FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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='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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5hbt|5hbt]]</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=5hbv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hbv OCA], [http://pdbe.org/5hbv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5hbv RCSB], [http://www.ebi.ac.uk/pdbsum/5hbv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5hbv ProSAT]</span></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Chrna1, Acra ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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=5hbv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hbv OCA], [http://pdbe.org/5hbv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5hbv RCSB], [http://www.ebi.ac.uk/pdbsum/5hbv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5hbv ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 19: / Line 20: @@
 </div>
 <div class="pdbe-citations 5hbv" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Bungarotoxin 3D structures|Bungarotoxin 3D structures]]
 == References ==
 <references/>
@@ Line 24: / Line 28: @@
 </StructureSection>
 [[Category: Bungarus multicinctus]]
+[[Category: Large Structures]]
+[[Category: Lk3 transgenic mice]]
 [[Category: Rattus norvegicus]]
 [[Category: Chen, L]]

5hbv

From Proteopedia

Revision as of 06:58, 20 May 2020

Complex structure of Fab35 and mouse nAChR alpha1

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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