The autoimmune TCR-Ob.2F3 can bind to MBP85-99/HLA-DR2 having an unconventional mode as in TCR-Ob.1A12.
The autoimmune TCR-Ob.2F3 can bind to MBP85-99/HLA-DR2 having an unconventional mode as in TCR-Ob.1A12.
复制标题
自身免疫TCR-Ob.2F3可以与MBP85-99/HLA-DR2结合，其具有如TCR-Ob.1A12中的非常规模式。
DOI：
10.1016/j.molimm.2010.07.010
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发表时间：
2010
影响因子：
3.6
通讯作者：
Strominger,JackL
中科院分区：
文献类型：
--
作者：
Kato,Zenichiro;Stern,JoelNH;Nakamura,HironoriK;Miyashita,Naoyuki;Kuwata,Kazuo;Kondo,Naomi;Strominger,JackL
T细胞受体（TCR）序列多样性的产生可以产生能够识别自身抗原的“禁止”克隆。在这里，髓鞘碱性蛋白肽（MBP85-99）、人白细胞抗原(HLA)-DR2 （DRB1*1501/DRA）和TCR-Ob之间的复合物结构。2F3是来自多发性硬化症（MS）患者的显性自身免疫克隆，已通过结构对接模拟和计算机动力学确定，并与TCR-Ob的结构进行了比较。通过x射线晶体学确定具有相同MHC/肽的1A12复合物。这两种TCRs在CDR3 α和β环中有三个氨基酸的不同。结果表明，在模拟结构的复合物中，两个CDR3β环与肽之间形成了不同的氢键，在TCR-Ob中可以看到三个氢键。2F3复合体和TCR-Ob中的5个。1 a12复杂。这两个tcr均位于HLA-DR2结合槽的n端附近，它们都具有正交的结合轴，但它们偏离约10°。本文使用的模拟方法，如结构对接和分子动力学，提供了一种有效和快速地理解分子结合模式的途径，而不是在已经有大型结构数据库的情况下获得多个晶体结构。
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.