Faull R J, Wang J, Leavesley D I, Puzon W, Russ G R, Vestweber D, Takada Y
Renal Unit, Royal Adelaide Hospital, North Terrace, Adelaide 5000, South Australia, Australia.
J Biol Chem. 1996 Oct 11;271(41):25099-106. doi: 10.1074/jbc.271.41.25099.
The functional status of an integrin depends on the conformation of its extracellular domain, which is controlled by the cell expressing that receptor. The transmission of regulatory signals from within the cell is considered to be via propagated conformational changes from the receptor's cytoplasmic tails to the extracellular ligand binding "pocket." The end result is increased accessibility of the ligand binding pocket in the high affinity ("active") form of integrins. We report a novel monoclonal antibody (QE.2E5) that binds within the cysteine-rich repeats in the integrin beta1 chain and induces high affinity binding of fibronectin to the integrin alpha5beta1. The QE.2E5 epitope is located approximately 200 residues both from the predicted binding site for fibronectin and from the epitopes recognized by other activating anti-beta1 monoclonal antibodies. It is also expressed on beta1 integrins from a number of nonhuman species. Although they have the same functional effects, the binding of QE.2E5 and another activating antibody (8A2) to the receptor have contrasting effects on the expression of an activation-dependent epitope in the beta1 chain. We propose that the cysteine-rich repeats contain a regulatory region that is distinct from those previously described in the integrin beta1 chain.
整合素的功能状态取决于其细胞外结构域的构象，而这一构象由表达该受体的细胞控制。细胞内调节信号的传递被认为是通过从受体的细胞质尾部到细胞外配体结合“口袋”的构象变化传播来实现的。最终结果是整合素以高亲和力（“活性”）形式时，其配体结合口袋的可及性增加。我们报道了一种新型单克隆抗体（QE.2E5），它结合在整合素β1链富含半胱氨酸的重复序列内，并诱导纤连蛋白与整合素α5β1的高亲和力结合。QE.2E5表位距离纤连蛋白的预测结合位点以及其他激活抗β1单克隆抗体识别的表位均约200个残基。它也在多种非人类物种的β1整合素上表达。尽管它们具有相同的功能效应，但QE.2E5和另一种激活抗体（8A2）与受体的结合对β1链中激活依赖性表位的表达具有相反的影响。我们提出富含半胱氨酸的重复序列包含一个与整合素β1链中先前描述的调节区域不同的调节区域。
