CONFORMATIONAL ISOMERISM AND THE DIVERSITY OF ANTIBODIES

被引:227
作者
FOOTE, J [1 ]
MILSTEIN, C [1 ]
机构
[1] MRC, MOLEC BIOL LAB, CAMBRIDGE CB2 2QH, ENGLAND
关键词
D O I
10.1073/pnas.91.22.10370
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The fact that one cell encodes a single antibody sequence does not necessarily mean that the resulting antibody folds into a single structure, although this is a common assumption. Here we challenge this view and suggest that many antibodies do not have a single conformation at the combining site. The basis for this proposal comes from the kinetic analysis of a set of murine hybridomas derived from defined stages of the immune response to 2-phenyl-5-oxazolone (Ox). Among them we have identified three antibodies that exhibit complex hapten-binding kinetics. We observed biphasic or triphasic reactions in stopped-flow fluorescence experiments, indicating that ligand binding involved isomerization, as well as associative steps. The existence of an equilibrium between at least two antibody conformations, with ligands binding preferentially to one form, was deduced from the variation with hapten concentration of the apparent rate of each phase.
引用
收藏
页码:10370 / 10374
页数:5
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