Distinct ligand-binding modes for integrin αvβ3-mediated adhesion to fibronectin versus vitronectin
Distinct ligand-binding modes for integrin αvβ3-mediated adhesion to fibronectin versus vitronectin
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DOI：
10.1074/jbc.m103997200
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发表时间：
2001-08-24
影响因子：
4.8
通讯作者：
Huber, F
中科院分区：
文献类型：
--
作者：
Boettiger, D;Lynch, L;Huber, F
细胞表面整合素可以响应配体结合和细胞内信号而采取不同的构象。几种整合素，包括alpha（v）beta（3）。可以与多个配体结合。将α（v）β（3）与纤连蛋白和玻连蛋白的结合用作模型，以确定在与两种不同配体的强结合中是否利用相同或不同形式的受体。使用旋转盘装置来测量α（v）β（3）-配体键的相对强度。两种配体的初始结合反应发生在没有代谢能量的情况下，并导致与纤连蛋白的强粘附，但与玻连蛋白的弱粘附。α（v）β（3）-玻连蛋白键强度的增加需要β（3）胞质结构域、胞内信号的磷酸化以及细胞骨架蛋白与由Tyr-747和Tyr-759控制的β（3）胞质结构域的结合。相比之下，α（v）β（3）介导的与纤连蛋白的粘附不受佛波醇12-肉豆蔻酸酯13-乙酸酯、Tyr-747和Tyr-759突变为苯丙氨酸或代谢能量的影响。这表明与纤连蛋白的强粘附使用初始结合构象，而与玻连蛋白的强结合需要信号诱导的α（v）β（3）构象的变化。
Cell surface integrins can adopt distinct conformations in response to ligand binding and intracellular signals. Several integrins including alpha (v)beta (3). can bind to multiple ligands. The binding of alpha (v)beta (3) to fibronectin and vitronectin was used as a model to determine whether the same or distinct forms of the receptor were utilized in strong binding to the two different ligands. A spinning-dise device was used to measure the relative strength of the alpha (v)beta (3)-ligand bonds. The initial binding reaction for both ligands occurred in the absence of metabolic energy and resulted in a strong adhesion to fibronectin but a weak adhesion to vitronectin. Increases in the strength of the alpha (v)beta (3)-vitronectin bond required phosphorylation of the 13, cytoplasmic domain, intracellular signals, and the binding of cytoskeletal proteins to cytoplasmic domains of beta (3) controlled by Tyr-747 and Tyr-759. In contrast, alpha (v)beta (3)-mediated adhesion to fibronectin was unaffected by phorbol 12-myristate 13-acetate, mutations of Tyr-747 and Tyr-759 to phenylalanine, or availability of metabolic energy. This suggests that strong adhesion to fibronectin used the initial binding conformation, whereas strong binding to vitronectin required signaling-induced changes in the conformation of alpha (v)beta (3).