Amino Acid Residues in the PSI Domain and Cysteine-rich Repeats of the Integrin β2 Subunit That Restrain Activation of the Integrin αxβ2 *
Amino Acid Residues in the PSI Domain and Cysteine-rich Repeats of the Integrin β2 Subunit That Restrain Activation of the Integrin αxβ2 *
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DOI：
10.1074/jbc.m005868200
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发表时间：
2001-03
期刊：
影响因子：
--
通讯作者：
Q. Zang;T. Springer
中科院分区：
文献类型：
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作者：
Q. Zang;T. Springer
白细胞整联蛋白αXβ2（p150，95）识别iC 3b补体片段，并作为补体受体4型发挥功能。αXβ2比其他β2整联蛋白更耐活化，并且在转染细胞中无活性。然而，当人αX与鸡或小鼠β2配对时，αXβ2被激活与iC 3b结合。激活取代被映射到单个残基或残基组的N-末端丛蛋白/信号蛋白/整联蛋白（PSI）结构域和C-末端富含半胱氨酸的重复2和3。这些区域通过长程二硫键连接。PSI结构域中的取代与富含半胱氨酸的重复序列中的取代协同作用。取代T4 P、T22 A、Q525 S和V526 L得到完全活化。与iC 3b结合的活化与富含半胱氨酸的重复序列3中CBR LFA-1/2表位的暴露相关。数据表明，激活取代存在于界面中，该界面将人αX/人β2整联蛋白抑制在非活性状态。该界面的开放与激活配体结合的其他结构域中的结构重排有关。
The leukocyte integrin αXβ2 (p150,95) recognizes the iC3b complement fragment and functions as the complement receptor type 4. αXβ2 is more resistant to activation than other β2 integrins and is inactive in transfected cells. However, when human αX is paired with chicken or mouse β2, αXβ2 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 αX/human β2 integrin in the inactive state. The opening of this interface is linked to structural rearrangements in other domains that activate ligand binding.