The I domain of integrin LFA-1 interacts with ICAM-1 domain 1 at residue Glu-34 but not Gln-73
The I domain of integrin LFA-1 interacts with ICAM-1 domain 1 at residue Glu-34 but not Gln-73
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DOI：
10.1074/jbc.273.6.3358
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发表时间：
1998-02-06
影响因子：
4.8
通讯作者：
Hogg, N
中科院分区：
文献类型：
--
作者：
Stanley, P;Hogg, N
使用固相测定，我们表明分离的 LFA-1 I 结构域以 Mg2+ 依赖性方式结合 ICAM-1，并被抗 I 结构域单克隆抗体阻断。该活性反映了完整受体的活性（Dransfield, I.、Cabanas, C.、Craig, A. 和 Hogg, N. (1992) J. Cell Biob. 116, 219-226），并表明 I 结构域控制二价阳离子依赖性受体功能。在 ICAM-1 中，结构域 1 残基 Glu-34 和 Gln-73 已被鉴定为对于作为完整受体的 LFA-1 的结合至关重要（Staunton, D. E.、Dustin, M. L.、Erickson, H. P. 和 Springer, T. A. (1990) Cell 61, 243-254）。我们首次表明，分离的 I 结构域与 ICAM-1 的结构域 1 结合，并且这种相互作用部分地被 Glu-34 突变抑制，但不被 Gln-73 突变抑制。抗 ICAM-1 单克隆抗体 RR1/1 映射到 Gln-73（Staunton, D. E.、Dustin, M. L.、Erickson, H. P. 和 Springer, T. A. (1990) Cell 61, 243-254），增强 I 结构域结合，表明该区域具有潜在的变构控制或协调结合。最后，Glu-34 ICAM-1 突变抑制的 I 结构域结合与二价阳离子依赖性相关，表明该残基可能与金属离子依赖性粘附位点直接接触。因此，我们描述了 LFA-1 I 结构域和 ICAM-1 之间的相互作用，这是一个控制完整受体功能但仅包括完整配体结合位点的一部分的事件。
Using a solid phase assay, we show that isolated LFA-1 I domain binds ICAM-1 in a Mg2+-dependent manner and is blocked by anti-I domain monoclonal antibodies. This activity mirrors that of the intact receptor (Dransfield, I., Cabanas, C., Craig, A., and Hogg, N. (1992) J. Cell Biob. 116, 219-226) and suggests that the I domain controls divalent cation-dependent receptor function. In ICAM-1, domain 1 residues Glu-34 and Gln-73 have been identified as critical for binding of LFA-1 as an intact receptor (Staunton, D. E., Dustin, M. L., Erickson, H. P., and Springer, T. A. (1990) Cell 61, 243-254). For the first time, we show that isolated I domain binds to domain 1 of ICAM-1 and that this interaction is inhibited partially by mutation of Glu-34 but not by Gln-73. The anti-ICAM-1 monoclonal antibody RR1/1, which maps to Gln-73 (Staunton, D. E., Dustin, M. L., Erickson, H. P., and Springer, T. A. (1990) Cell 61, 243-254), enhances I domain binding, suggesting potential allosteric control or coordinate binding by this region. Finally, I domain binding inhibited by Glu-34 ICAM-1 mutation correlates with divalent cation dependence, indicating that this residue might be in direct contact with the metal ion-dependent adhesion site. Thus, we describe the interaction between the LFA-1 I domain and ICAM-1, an event that controls the function of the intact receptor but includes only part of the complete ligand binding site.