免疫球蛋白VL结构域互补决定区中的不稳定环交换。
Destabilizing loop swaps in the CDRs of an immunoglobulin VL domain.
作者信息
Helms L R, Wetzel R
机构信息
Macromolecular Sciences Department, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406, USA.
出版信息
Protein Sci. 1995 Oct;4(10):2073-81. doi: 10.1002/pro.5560041012.
Abstract
It is generally believed that loop regions in globular proteins, and particularly hypervariable loops in immunoglobulins, can accommodate a wide variety of sequence changes without jeopardizing protein structure or stability. We show here, however, that novel sequences introduced within complementarity determining regions (CDRs) 1 and 3 of the immunoglobulin variable domain REI VL can significantly diminish the stability of the native state of this protein. Besides their implications for the general role of loops in the stability of globular proteins, these results suggest previously unrecognized stability constraints on the variability of CDRs that may impact efforts to engineer new and improved activities into antibodies.
摘要
一般认为，球状蛋白质中的环区，尤其是免疫球蛋白中的高变环，能够容纳各种各样的序列变化而不危及蛋白质结构或稳定性。然而，我们在此表明，引入免疫球蛋白可变结构域REI VL的互补决定区（CDR）1和3内的新序列可显著降低该蛋白质天然状态的稳定性。除了对环区在球状蛋白质稳定性中的一般作用有影响外，这些结果还表明了对CDR变异性以前未被认识到的稳定性限制，这可能会影响将新的和改进的活性引入抗体的工程化努力。
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