Ligand-binding specificities of laminin-binding integrins:: A comprehensive survey of laminin-integrin interactions using recombinant α3β1, α6β1, α7β1 and α6β4 integrins
Ligand-binding specificities of laminin-binding integrins:: A comprehensive survey of laminin-integrin interactions using recombinant α3β1, α6β1, α7β1 and α6β4 integrins
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DOI：
10.1016/j.matbio.2005.12.001
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发表时间：
2006-04-01
期刊：
影响因子：
6.9
通讯作者：
Sekiguchi, K
中科院分区：
文献类型：
--
作者：
Nishiuchi, R;Takagi, J;Sekiguchi, K
细胞与基底膜的相互作用主要通过一组整联蛋白家族蛋白质（包括整联蛋白α 3 β 1、α 6 β 1、α 7 β 1和α 6 β 4）与层粘连蛋白的接合来介导。为了探索这些层粘连蛋白结合整联蛋白的配体结合特异性，我们产生了这些整联蛋白，包括两种α 7 β 1剪接变体（α 7 X 1 β 1和α 7 X 2 β 1），作为可溶性重组蛋白，并确定了它们对一组含有不同α链的纯化层粘连蛋白同种型的结合特异性和亲和力。在所研究的五种层粘连蛋白结合整合素中，α 3 β 1和α 6 β 4对层粘连蛋白-332表现出明显的特异性（α 3 β 3 γ 2）和层粘连蛋白-511（（α 5 β 1 γ 1）/521（α 5 β 2 γ 1），而整合素α 6 β 1显示出广泛的特异性，结合所有层粘连蛋白同种型，优选层粘连蛋白-111（α 1 β 1 γ 1）、层粘连蛋白-332和层粘连蛋白-511/521。两种α 7 β 1变体与α 3 β 1、α 6 β 1和α 6 β 4的不同之处在于它们不结合层粘连蛋白-332。α 7 X 1 β 1结合所有层粘连蛋白，除了层粘连蛋白332，优先结合层粘连蛋白211（α 2 β 1 γ 1）/221（α 2 β 2 γ 1）和层粘连蛋白511/521，而α 7 X 2 β 1优先结合层粘连蛋白111和层粘连蛋白211/221。层粘连蛋白-511/521是所有层粘连蛋白结合整联蛋白的最优选配体，除了α 7 X 2 β 1，而层粘连蛋白-411是最差的配体，能够仅以适度的结合亲和力结合α 6 β 1和α 7 X 1 β 1。层粘连蛋白结合整合素和一组层粘连蛋白之间的相互作用的这些全面的分析清楚地表明，整合素和层粘连蛋白的同种型在它们的结合特异性和亲和力方面不同，并提供了分子基础，以更好地理解细胞与限定的层粘连蛋白组合物的基底膜的粘附相互作用。(c)2005年Elsevier B. V./国际矩阵生物学会。All rights reserved.
The interactions of cells with basement membranes are primarily mediated via the engagement of laminins by a group of integrin family proteins, including integrins alpha 3 beta 1, alpha 6 beta 1, alpha 7 beta 1 and alpha 6 beta 4. To explore the ligand-binding specificities of these laminin-binding integrins, we produced these integrins, including two alpha 7 beta 1 splice variants (alpha 7X1 beta 1 and alpha 7X2 beta 1), as soluble recombinant proteins and determined their binding specificities and affinities toward a panel of purified laminin isoforms containing distinct a chains. Among the five laminin-binding integrins investigated, alpha 3 beta 1 and alpha 6 beta 4 exhibited a clear specificity for laminin-332 (alpha 3 beta 3 gamma 2) and laminin-511 ((alpha 5 beta 1 gamma 1)/521 (alpha 5 beta 2 gamma 1), while integrin alpha 6 beta 1 showed a broad specificity, binding to all laminin isoforms with a preference for laminin-111 (alpha 1 beta 1 gamma 1), laminin-332 and laminin-511/521. The two alpha 7 beta 1 variants were distinct from alpha 3 beta 1,alpha 6 beta 1 and alpha 6 beta 4 in that they did not bind to laminin-332. alpha 7X1 beta 1 bound to all laminins, except laminin-332, with a preference for laminin-211 (alpha 2 beta 1 gamma 1)/221 (alpha 2 beta 2 gamma 1) and laminin-511/521, while alpha 7X2 beta 1 bound preferentially to laminin-111 and laminin-211/221. Laminin-511/521 was the most preferred ligand for all the laminin-binding integrins, except for alpha 7X2 beta 1 whereas laminin-411 was the poorest ligand, capable of binding to alpha 6 beta 1 and alpha 7X1 beta 1 with only modest binding affinities. These comprehensive analyses of the interactions between laminin-binding integrins and a panel of laminins clearly demonstrate that the isoforms of both integrins and laminins differ in their binding specificities and affinities, and provide a molecular basis for better understanding of the adhesive interactions of cells with basement membranes of defined laminin compositions. (c) 2005 Elsevier B.V./Intemational Society of Matrix Biology. All rights reserved.