Integrin 41-Dependent Adhesion to ADAM 28 (MDC-L)
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- 作者：Lance C. Bridges ; Krista R. Hanson ; Patricia H. Tani ; Timothy Mather ; and Ron D. Bowditch
- 刊名：Biochemistry
- 出版年：2003
- 出版时间：April 8, 2003
- 年：2003
- 卷：42
- 期：13
- 页码：3734 - 3741
- 全文大小：301K
- 年卷期：v.42,no.13(April 8, 2003)
- ISSN：1520-4995
文摘
ADAMs (a disintegrin and metalloprotease) are a family of proteins that possess functionaladhesive and proteolytic domains. ADAM 28 (MDC-L) is expressed by human lymphocytes and containsa disintegrin-like domain that serves as a ligand for the leukocyte integrin, 
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1. To elucidate whichresidues comprise the 41 binding site in the ADAM 28 disintegrin domain, a charge-to-alaninemutagenesis strategy was utilized. Each alanine substitution mutant was evaluated and compared to thenative sequence for its ability to support cell adhesion of the T-lymphoma cell line, Jurkat. This approachidentified ADAM 28 residues Lys437, Lys442, Lys455, Lys459, Lys460, Lys469, and Glu476 as being essentialfor 41-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 venomdisintegrins suggested that residues contributing to 41 recognition are aligned on one face of the domain.This study demonstrates that residues located outside of the disintegrin loop participate in integrinrecognition of mammalian disintegrins.
41. To elucidate whichresidues comprise the 41 binding site in the ADAM 28 disintegrin domain, a charge-to-alaninemutagenesis strategy was utilized. Each alanine substitution mutant was evaluated and compared to thenative sequence for its ability to support cell adhesion of the T-lymphoma cell line, Jurkat. This approachidentified ADAM 28 residues Lys437, Lys442, Lys455, Lys459, Lys460, Lys469, and Glu476 as being essentialfor 41-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 venomdisintegrins suggested that residues contributing to 41 recognition are aligned on one face of the domain.This study demonstrates that residues located outside of the disintegrin loop participate in integrinrecognition of mammalian disintegrins.