Structural differences between HLA-DQ molecules associated with myasthenia gravis characterized by molecular modeling.
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.
Hjelmström
P
P
Department of Molecular Medicine, Karolinska Hospital, Karolinska Institute, Stockholm, Sweden.
DeWeese-Scott
C
C
Penzotti
J E
JE
Lybrand
T P
TP
Sanjeevi
C B
CB
D006683:HLA-DQ Antigens / Q000032:analysis* / Q000235:genetics*; D006801:Humans; D008958:Models, Molecular; D009157:Myasthenia Gravis / Q000276:immunology*
D006683:HLA-DQ Antigens; C053186:HLA-DQ2 antigen; C063831:HLA-DQ6 antigen