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首页> 外文期刊>Biochemistry >Integrin alpha 4 beta 1-dependent adhesion to ADAM 28 (MDC-L) requires an extended surface of the disintegrin domain
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Integrin alpha 4 beta 1-dependent adhesion to ADAM 28 (MDC-L) requires an extended surface of the disintegrin domain

机译：整合素α4 beta 1依赖ADAM 28（MDC-L）的粘附需要整合素域的扩展表面

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摘要

ADAMS (a disintegrin and metalloprotease) are a family of proteins that possess functional adhesive and proteolytic domains. ADAM 28 (MDC-L) is expressed by human lymphocytes and contains a disintegrin-like domain that serves as a ligand for the leukocyte integrin, alpha4beta1. To elucidate which residues comprise the alpha4beta1 binding site in the ADAM 28 disintegrin domain, a charge-to-alanine mutagenesis strategy was utilized. Each alanine substitution mutant was evaluated and compared to the native sequence for its ability to support cell adhesion of the T-lymphoma cell line, Jurkat. This approach identified ADAM 28 residues Lys(437), Lys(442), Lys(411), Lys(419), Lys(460), Lys(469), and Glu(476) as being essential for alpha4beta1-dependent cell adhesion. The epitope for a function-blocking monoclonal antibody, Dis 1-1, was localized to the N-terminal end of the ADAM 28 disintegrin domain using these same charge-to-alanine mutants. Three distinct molecular models based upon the known structures of snake venom disintegrins suggested that residues contributing to alpha4beta1 recognition are aligned on one face of the domain. This study demonstrates that residues located outside of the disintegrin loop participate in integrin recognition of mammalian disintegrins. [References: 50]
机译：ADAMS（一种整合素和金属蛋白酶）是具有功能性黏附和蛋白水解结构域的蛋白质家族。 ADAM 28（MDC-L）由人淋巴细胞表达，并包含一个像整联蛋白样的结构域，该结构域可作为白细胞整联蛋白alpha4beta1的配体。为了阐明ADAM 28 Disintegrin域中哪些残基包含alpha4beta1结合位点，采用了电荷-丙氨酸诱变策略。评价每种丙氨酸取代突变体，并将其与天然序列比较，以支持其支持T淋巴瘤细胞系Jurkat的细胞粘附。该方法确定了ADAM 28个残基Lys（437），Lys（442），Lys（411），Lys（419），Lys（460），Lys（469）和Glu（476）是alpha4beta1依赖性细胞粘附所必需的。使用这些相同的电荷-丙氨酸突变体，功能阻断性单克隆抗体Dis 1-1的表位位于ADAM 28 disintegrin域的N末端。基于蛇毒双整合蛋白的已知结构的三种不同的分子模型表明，有助于alpha4beta1识别的残基在结构域的一侧对齐。这项研究表明，位于整合素环之外的残基参与了哺乳动物整合素的整合素识别。 [参考：50]

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