Evidence for plasticity and structural mimicry at the immunoglobulin light chain-protein L interface
Evidence for plasticity and structural mimicry at the immunoglobulin light chain-protein L interface
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DOI：
10.1074/jbc.m206105200
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发表时间：
2002-12-06
影响因子：
4.8
通讯作者：
Stura, EA
中科院分区：
文献类型：
--
作者：
Graille, M;Harrison, S;Stura, EA
多结构域细菌表面蛋白 L (PpL) 是仅 10% 的消化链球菌菌株表达的毒力因子，其表达与细菌性阴道病相关。最近通过 X 射线晶体学描述了其识别 60% 哺乳动物免疫球蛋白轻链可变区 (V-L) 的分子基础，这表明每个蛋白质 L 结构域上存在两个 V-L 结合位点（Graille, M.、Stura, E. A.、Housden, N.G.、Beekingham, J.A.、Bottomley, S. P.、Beale, D.、Taussig, M.J.， Sutton, B.J.、Gore, M. G. 和 Charbonnier, J. (2001) 结构，679-687)。在这里，我们报告了与 Fab' 片段复合的蛋白质 L 突变体在 2.1 埃分辨率下的晶体结构，其中仅 50% 的 VL 残基与保守的 PpL 位点 1 相互作用。两种结构的位点 1 界面的比较显示了 L 蛋白如何能够适应这些序列差异，从而与大量 Ig 结合。 X 射线结构和 NMR 结果证实单个蛋白质 L 结构域上存在两个 V-L 结合位点。这些位点表现出生长因子与其受体结合的显着结构模拟。这可以解释 L 蛋白对人类 B 淋巴细胞的超抗原活性。
The multidomain bacterial surface protein L (PpL) is a virulence factor expressed by only 10% of Peptostreptococcus magnus strains, and its expression is correlated with bacterial vaginosis. The molecular basis for its ability to recognize 60% of mammalian immunoglobulin light chain variable regions (V-L) has been described recently by x-ray crystallography, which suggested the presence of two V-L binding sites on each protein L domain (Graille, M., Stura, E. A., Housden, N.G., Beekingham, J.A., Bottomley, S. P., Beale, D., Taussig, M.J., Sutton, B.J., Gore, M. G., and Charbonnier, J. (2001) Structure, 679-687). Here, we report the crystal structure at 2.1 Angstrom resolution of a protein L mutant complexed to an Fab' fragment with only 50% of the VL residues interacting with PpL site 1 conserved. Comparison of the site 1 interface from both structures shows how protein L is able to accommodate these sequence differences and therefore bind to a large repertoire of Ig. The x-ray structure and NMR results confirm the existence of two V-L binding sites on a single protein L domain. These sites exhibit a remarkable structural mimicry of growth factors binding to their receptors. This could explain the protein L superantigenic activity on human B lymphocytes.