کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2832023 1570739 2010 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
The autoimmune TCR-Ob.2F3 can bind to MBP85–99/HLA-DR2 having an unconventional mode as in TCR-Ob.1A12
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شناسی مولکولی
پیش نمایش صفحه اول مقاله
The autoimmune TCR-Ob.2F3 can bind to MBP85–99/HLA-DR2 having an unconventional mode as in TCR-Ob.1A12
چکیده انگلیسی

The generation of T cell receptor (TCR) sequence diversity can produce ‘forbidden’ clones able to recognize self-antigens. Here, the structure of the complex between a myelin basic protein peptide (MBP85–99), human leukocyte antigen (HLA)-DR2 (DRB1*1501/DRA) and TCR-Ob.2F3, the dominant autoimmune clone obtained from a multiple sclerosis (MS) patient, has been determined using structural docking simulation and dynamics in silico and compared to the structure of TCR-Ob.1A12 complexes with the same MHC/peptide determined by X-ray crystallography. The two TCRs differ by three amino acids in the CDR3 α and β loops. As the result different hydrogen bonds are formed between the two CDR3β loops and the peptide in the complexes of the simulated structures, with three hydrogen bonds seen in the TCR-Ob.2F3 complex and five in the TCR-Ob.1A12 complex. The two TCRs, each located near the N-terminal end of the HLA-DR2 binding groove and both had an orthogonal binding axis but they deviated by about 10°. Simulation methods, such as structural docking and molecular dynamics as used here, provide an avenue to understand molecular binding mode efficiently and more rapidly than obtaining multiple crystal structures when a large structural database is already available.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular Immunology - Volume 48, Issues 1–3, November–December 2010, Pages 314–320
نویسندگان
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