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10.7554/eLife.23043 http://scihub22266oqcxt.onion/10.7554/eLife.23043 C5404922!5404922!28440223     free     free     free Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       eLife 2017 ; 6 (ä): ä Nephropedia Template TP {{tp|p=28440223|t=2017. Structural insights into the molecular mechanisms of myasthenia gravis and their therapeutic implications |pdf=|usr=}}{{28440223}} gab.com Text Structural insights into the molecular mechanisms of myasthenia gravis and their therapeutic implications JO: eLife http://www.kidney.de/pget.php?&tw=1&pmid=28440223 #FOAvip 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 ?1 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 ?1. 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.DOI:http://dx.doi.org/10.7554/eLife.23043.001 Twit Text FOAVip Structural insights into the molecular mechanisms of myasthenia gravis and their therapeutic implications ????eLife http://www.kidney.de/pget.php?&tw=1&pmid=28440223 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=28440223 #FOAvip English Wikipedia <ref>{{Cite pmid|28440223}}</ref> Structural insights into the molecular mechanisms of myasthenia gravis and their therapeutic implications #MMPMID28440223 Noridomi K; Watanabe G; Hansen MN; Han GW; Chen L eLife 2017[]; 6 (ä): ä PMID28440223show ga 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 ?1 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 ?1. 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.DOI:http://dx.doi.org/10.7554/eLife.23043.001 äStructural insights into the molecular mechanisms of myasthenia gravis(epmc).pdf DeepDyve Pubget Overpricing