Biological Activities of the Homologous Loop Regions in the Laminin 伪 Chain LG Modules

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• 作者：Fumihiko Katagiri ; Toshihiro Hara ; Yuji Yamada ; Shunsuke Urushibata ; Kentaro Hozumi ; Yamato Kikkawa ; Motoyoshi Nomizu
• 刊名：Biochemistry
• 出版年：2014
• 出版时间：June 10, 2014
• 年：2014
• 卷：53
• 期：22
• 页码：3699-3708
• 全文大小：817K
• 年卷期：v.53,no.22(June 10, 2014)
• ISSN：1520-4995

文摘

Each laminin 伪 chain (伪1鈭捨? chains) has chain-specific diverse biological functions. The C-terminal globular domain of the 伪 chain consists of five laminin-like globular (LG1鈥?) modules and plays a critical role in biological activities. The LG modules consist of a 14-stranded 尾-sheet (A鈥揘) sandwich structure. Previously, we described the chain-specific biological activities of the loop regions between the E and F strands in the LG4 modules using five homologous peptides (G4EF1鈥揋4EF5). Here, we further analyze the biological activities of the E鈥揊 strands loop regions in the rest of LG modules. We designed 20 homologous peptides (approximately 20 amino acid length), and 17 soluble peptides were used for the cell attachment assay. Thirteen peptides promoted cell attachment activity with different cell morphologies. Cell attachment to peptides G1EF1, G1EF2, G2EF1, G3EF4, and G5EF4 was inhibited by heparin, and peptides G1EF1, G1EF2, and G2EF1 specifically bound to syndecan-overexpressing cells. Cell attachment to peptides G2EF3, G3EF1, G3EF3, G5EF1, G5EF3, and G5EF5 was inhibited EDTA. Further, cell attachment to peptides G3EF3, G5EF1, and G5EF5 was inhibited by both anti-integrin 伪2 and 尾1 antibodies, whereas cell attachment to peptide G5EF3 was inhibited by only anti-integrin 尾1 antibody. Cell attachment to peptides G1EF4, G3EF4, and G5EF4 was inhibited by both heparin and EDTA and was not inhibited by anti-integrin antibodies. The active peptide sequence alignments suggest that the syndecan-binding peptides contain a 鈥渂asic amino acid (BAA)-Gly-BAA鈥?motif in the middle of the molecule and that the integrin-binding peptides contain an 鈥渁cidic amino acid (AAA)鈥?Gly-BAA motif. Core-switched peptide analyses suggested that the 鈥淏AA-Gly-BAA鈥?motif is critical for binding to syndecans and that the 鈥淎AA-Gly-BAA鈥?motif has potential to recognize integrins. These findings are useful for understanding chain-specific biological activities of laminins and to evaluate receptor-specific binding mechanisms.