title: Structural differences between HLA-DQ molecules associated with myasthenia gravis characterized by molecular modeling.
abstract: Myasthenia gravis (MG) is characterized by muscle weakness due to autoimmunity against the nicotinic acetylcholine receptor (nAChR). MG is associated with polymorphisms in HLA-DQ genes and the aim of the present study was to characterize structural differences in the peptide binding groove of HLA-DQ molecules positively and negatively associated with MG. Three dimensional models of the positively associated DQ2 (DQB1*02) and negatively associated DQ6 (DQB1*0603) molecules were constructed by homology modeling techniques. The differences in peptide binding properties were primarily localized to peptide-anchor pockets P7 and P9, which might be of importance for the binding of disease-associated peptides from the nAChR.
authors.affiliation: Department of Molecular Medicine, Karolinska Hospital, Karolinska Institute, Stockholm, Sweden.
authors.forename: P
authors.initials: P
authors.lastname: Hjelmström
authors.forename: C
authors.initials: C
authors.lastname: DeWeese-Scott
authors.forename: J E
authors.initials: JE
authors.lastname: Penzotti
authors.forename: T P
authors.initials: TP
authors.lastname: Lybrand
authors.forename: C B
authors.initials: CB
authors.lastname: Sanjeevi
mesh_terms: D006683:HLA-DQ Antigens / Q000032:analysis* / Q000235:genetics*; D006801:Humans; D008958:Models, Molecular; D009157:Myasthenia Gravis / Q000276:immunology*
chemical_list: D006683:HLA-DQ Antigens; C053186:HLA-DQ2 antigen; C063831:HLA-DQ6 antigen