Alpha 3 beta 1 adhesion to laminin-5 and invasin: critical and differential role of integrin residues clustered at the boundary between alpha 3 N-terminal repeats 2 and 3.
Alpha 3 beta 1 adhesion to laminin-5 and invasin: critical and differential role of integrin residues clustered at the boundary between alpha 3 N-terminal repeats 2 and 3.
复制标题
α 3 β 1 与层粘连蛋白 5 和侵袭素的粘附：聚集在 α 3 N 端重复序列 2 和 3 之间边界处的整联蛋白残基的关键和差异作用。
DOI：
10.1021/bi990323b
复制
发表时间：
1999
期刊：
影响因子：
2.9
通讯作者：
Takada,Y
中科院分区：
文献类型：
--
作者：
Zhang,XP;Puzon-McLaughlin,W;Irie,A;Kovach,N;Prokopishyn,NL;Laferté,S;Takeuchi,K;Tsuji,T;Takada,Y
Integrin/ligand interaction is a therapeutic target for many diseases. We previously reported that residues critical for ligand binding are clustered in N-terminal repeat 3 (in the predicted 2-3 loop) of α4, α5 and αIIb. Here we have localized residues critical for ligand binding in the α3 subunit of integrin α3β1 with distinct ligand specificity (laminin-5). We identified an α3 epitope common to several function-blocking anti-α3 antibodies at the boundary between repeats 1 and 2 (residues 75−80). We found that swapping the predicted 4-1 loop (residues 153−165) at the boundary between repeats 2 and 3 with the corresponding α4 sequence and mutating Thr-162 and Gly-163 residues in this predicted loop block laminin-5 binding. Thr-162 and Gly-163 and the antibody epitope are separated in the primary structure; however, they are close to each other in the proposed β-propeller model. Mutating residues recently reported to block (Tyr-186 and Trp-188) or enhance (Asp-122) laminin-5 binding to α3β1 [Krukonis, E. S., Dersch, P., Eble, J. A., and Isberg, R. R.(1998)J. Biol. Chem. 273, 31837−31843] did not affect laminin-5 binding under the assay conditions used. Thr-162 and Gly-163 are not critical for adhesion to invasin, indicating that laminin-5 and invasin may use different recognition mechanisms, and that mutation of Thr-162 and Gly-163 does not drastically affect the integrity of α3β1. These results suggest that residues critical for ligand binding may be similarly (but not identically) located in repeat 3 of the α subunit regardless of ligand specificity.
