5hbt

Complex structure of Fab35 and human nAChR alpha1Complex 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Acetyl choline receptor 3D structures Bungarotoxin 3D structures

spinqualitylabelsall models 5hbt, resolution 2.61Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image