Structure of the Calx-β domain of the integrin β4 subunit: insights into function and cation-independent stability
Structure of the Calx-β domain of the integrin β4 subunit: insights into function and cation-independent stability
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DOI：
10.1107/s0907444909018745
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发表时间：
2009-08-01
影响因子：
2.2
通讯作者：
de Pereda, Jose M.
中科院分区：
文献类型：
--
作者：
Alonso-Garcia, Noelia;Ingles-Prieto, Alvaro;de Pereda, Jose M.
整合素α 6 β 4是层粘连蛋白的受体，并提供上皮细胞与基底膜的稳定粘附。此外，α 6 β 4对于伤口愈合期间的角质形成细胞迁移是重要的，并且有利于癌侵入周围组织。β 4亚基的胞质结构域负责整联蛋白的大部分细胞内相互作用;它含有四个纤连蛋白III型结构域和一个Calx-β基序。β 4的Calx-β结构域的晶体结构被确定为1.48埃分辨率。该结构不含阳离子，生物物理数据支持β 4的Calx-β结构域不结合钙的假设。β 4的Calx-β结构域与Na+/Ca 2 +-交换器1的钙结合结构域的比较揭示，在β 4中Arg 1003占据与Na+/Ca 2 +-交换器中的钙离子的位置相等的位置。通过结合诱变和热诱导解折叠，表明Arg 1003有助于Calx-β结构域的稳定性。的钙蛋白β结构域的功能和细胞内的相互作用的整合素β 4亚基的背景下进行了讨论，并提出了一个推定的功能位点。
The integrin alpha 6 beta 4 is a receptor for laminins and provides stable adhesion of epithelial cells to the basement membranes. In addition, alpha 6 beta 4 is important for keratinocyte migration during wound healing and favours the invasion of carcinomas into surrounding tissue. The cytoplasmic domain of the beta 4 subunit is responsible for most of the intracellular interactions of the integrin; it contains four fibronectin type III domains and a Calx-beta motif. The crystal structure of the Calx-beta domain of beta 4 was determined to 1.48 angstrom resolution. The structure does not contain cations and biophysical data support the supposition that the Calx-beta domain of beta 4 does not bind calcium. Comparison of the Calx-beta domain of beta 4 with the calcium-binding domains of Na+/Ca2+-exchanger 1 reveals that in beta 4 Arg1003 occupies a position equivalent to that of the calcium ions in the Na+/Ca2+-exchanger. By combining mutagenesis and thermally induced unfolding, it is shown that Arg1003 contributes to the stability of the Calx-beta domain. The structure of the Calx-beta domain is discussed in the context of the function and intracellular interactions of the integrin beta 4 subunit and a putative functional site is proposed.