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  • 标题:Requirement of open headpiece conformation for activation of leukocyte integrin αXβ2
  • 本地全文:下载
  • 作者:Xing Chen ; Can Xie ; Noritaka Nishida
  • 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:2010
  • 卷号:107
  • 期号:33
  • 页码:14727-14732
  • DOI:10.1073/pnas.1008663107
  • 语种:English
  • 出版社:The National Academy of Sciences of the United States of America
  • 摘要:Negative stain electron microscopy (EM) and adhesion assays show that {alpha}X{beta}2 integrin activation requires headpiece opening as well as extension. An extension-inducing Fab to the {beta}2 leg, in combination with representative activating and inhibitory Fabs, were examined for effect on the equilibrium between the open and closed headpiece conformations. The two activating Fabs stabilized the open headpiece conformation. Conversely, two different inhibitory Fabs stabilized the closed headpiece conformation. Adhesion assays revealed that {alpha}X{beta}2 in the extended-open headpiece conformation had high affinity for ligand, whereas both the bent conformation and the extended-closed headpiece conformation represented the low affinity state. Intermediate integrin affinity appears to result not from a single conformational state, but from a mixture of equilibrating conformational states.
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