期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2004
卷号：101
期号：43
页码：15422-15427
DOI：10.1073/pnas.0406680101
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Two activation-dependent Abs to the integrin {alpha}L-subunit were used to study conformational rearrangement of {alpha}L{beta}2 on the cell surface. Activation lowered the concentration of Ca2+ required for maximal expression of each epitope. Each Ab requires the Ca2+-binding loop in the integrin genu and nearby species-specific residues in the thigh domain. Key thigh residues are shielded from Ab in the bent integrin conformation by the {alpha}-subunit calf-1 domain and the nearby bent {beta} leg, suggesting that extension at the genu is required for epitope exposure. Activating stimuli and {alpha}/{beta} I-like small molecule antagonists demonstrate that exposure of epitopes in the integrin {alpha}- and {beta}-subunit legs is coordinate during integrin activation. A coordinating residue donated by the calf-1 domain is as important as Ca2+ for mAb binding. Together with inspection of the {alpha}V structure, this result suggests that the genu/calf-1 interface is maintained in integrin activation, and that extension occurs by a rearrangement at the thigh/genu interface.
