Department of Pathology, Harvard Medical School, Immune Disease Institute, Children's Hospital Boston, Boston, MA 02115, USA.
Proc Natl Acad Sci U S A. 2010 Aug 17;107(33):14727-32. doi: 10.1073/pnas.1008663107. Epub 2010 Aug 2.
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.
负染电子显微镜（EM）和黏附实验表明，α(X)β(2)整合素的激活需要头部片段的打开和延伸。我们研究了针对β(2)腿的延伸诱导 Fab 以及有代表性的激活和抑制 Fab 对头部片段开放和闭合构象之间平衡的影响。两个激活 Fab 稳定了开放的头部片段构象。相反，两个不同的抑制 Fab 稳定了闭合的头部片段构象。黏附实验表明，处于延伸-开放头部片段构象的 α(X)β(2)对配体具有高亲和力，而弯曲构象和延伸-闭合头部片段构象则代表低亲和力状态。中间的整合素亲和力似乎不是来自单一的构象状态，而是来自平衡的构象状态的混合物。
