Zang Q, Springer T A
Center for Blood Research, Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA.
J Biol Chem. 2001 Mar 9;276(10):6922-9. doi: 10.1074/jbc.M005868200. Epub 2000 Nov 28.
The leukocyte integrin alpha(X)beta(2) (p150,95) recognizes the iC3b complement fragment and functions as the complement receptor type 4. alpha(X)beta(2) is more resistant to activation than other beta(2) integrins and is inactive in transfected cells. However, when human alpha(X) is paired with chicken or mouse beta(2), alpha(X)beta(2) is activated for binding to iC3b. Activating substitutions were mapped to individual residues or groups of residues in the N-terminal plexin/semaphorin/integrin (PSI) domain and C-terminal cysteine-rich repeats 2 and 3. These regions are linked by a long range disulfide bond. Substitutions in the PSI domain synergized with substitutions in the cysteine-rich repeats. Substitutions T4P, T22A, Q525S, and V526L gave full activation. Activation of binding to iC3b correlated with exposure of the CBR LFA-1/2 epitope in cysteine-rich repeat 3. The data suggest that the activating substitutions are present in an interface that restrains the human alpha(X)/human beta(2) integrin in the inactive state. The opening of this interface is linked to structural rearrangements in other domains that activate ligand binding.
白细胞整合素α(X)β(2)（p150,95）识别iC3b补体片段并作为4型补体受体发挥作用。α(X)β(2)比其他β(2)整合素对激活更具抗性，并且在转染细胞中无活性。然而，当人α(X)与鸡或小鼠β(2)配对时，α(X)β(2)被激活以结合iC3b。激活替代被定位到N端丛蛋白/信号素/整合素（PSI）结构域以及C端富含半胱氨酸的重复序列2和3中的单个残基或残基组。这些区域通过一个长程二硫键相连。PSI结构域中的替代与富含半胱氨酸重复序列中的替代协同作用。替代T4P、T22A、Q525S和V526L可实现完全激活。与iC3b结合的激活与富含半胱氨酸重复序列3中CBR LFA-1/2表位的暴露相关。数据表明，激活替代存在于一个界面中，该界面在非活性状态下限制人α(X)/人β(2)整合素。该界面的打开与激活配体结合的其他结构域中的结构重排相关。
