Antibody binding defines a structure for an epitope that participates in the PrPC → PrPSc conformational change
Antibody binding defines a structure for an epitope that participates in the PrPC → PrPSc conformational change
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DOI：
10.1006/jmbi.1999.3193
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发表时间：
1999-11-05
影响因子：
5.6
通讯作者：
Cohen, FE
中科院分区：
文献类型：
--
作者：
Kanyo, ZF;Pan, KM;Cohen, FE
抗叙利亚仓鼠朊病毒蛋白（SHaPrP）单克隆抗体Fab 3F 4单独的，以及与其同源肽表位（SHaPrP 104-113）的复合物的X射线晶体结构，已被确定为原子分辨率。十肽的构象为Ω环。在表位结合后，抗体结合区存在实质性改变。该肽结合在Fab表面上的U形凹槽中，两个特异性决定簇Met 109和Met 112深深穿透到由重链和轻链互补决定区形成的单独的疏水腔中。除了Fab和肽之间的大量接触之外，还观察到两个肽内氢键，这可能表明与Fab结合的结构在溶液中瞬时存在。这提供了在SHPrP 90-231、SHaPrP 29-231和小鼠PrP 23-231的NMR研究中观察到的PrP N-末端区域部分的第一个结构信息。PrPC和PrPSc的抗原表面的抗体表征将该柔性区域鉴定为构象重排的组分，构象重排是朊病毒疾病的基本特征。(C)北京：科学出版社.
The X-ray crystallographic structures of the anti-Syrian hamster prion protein (SHaPrP) monoclonal Fab 3F4 alone, as well as the complex with its cognate peptide epitope (SHaPrP 104-113), have been determined to atomic resolution. The conformation of the decapeptide is an Omega-loop. There are substantial alterations in the antibody combining region upon epitope binding. The peptide binds in a U-shaped groove on the Fab surface, with the two specificity determinants, Met109 and Met112 penetrating deeply into separate hydrophobic cavities formed by the heavy and light chain complementarity-determining regions. In addition to the numerous contacts between the Fab and the peptide, two intrapeptide hydrogen bonds are observed, perhaps indicating the structure bound to the Fab exists transiently in solution. This provides the first structural information on a portion of the PrP N-terminal region observed to be flexible in the NMR studies of SHPrP 90-231, SHaPrP 29-231 and mouse PrP 23-231. Antibody characterization of the antigenic surfaces of PrPC and PrPSc identifies this flexible region as a component of the conformational rearrangement that is an essential feature of prion disease. (C) 1999 Academic Press.