Biological activities of the homologous loop regions in the laminin α chain LG modules.
Biological activities of the homologous loop regions in the laminin α chain LG modules.
复制标题
层粘连蛋白 α 链 LG 模块中同源环区域的生物活性。
作者：
Fumihiko Katagiri;Toshihiro Hara;Yuji Yamada;S. Urushibata;K. Hozumi;Y. Kikkawa;M. Nomizu
层粘连蛋白α链（α1-α5链）具有链特异性的多种生物学功能。α链的C端球状结构域由5个层粘连蛋白样球状（LG 1 -5）模块组成，在生物活性中起着关键作用。LG模块由14股β-折叠（A-N）夹层结构组成。先前，我们描述了使用五种同源肽（G4 EF 1-G4 EF 5）的LG 4模块中E和F链之间的环区域的链特异性生物活性。在这里，我们进一步分析了LG模块的其余部分中的E-F链环区域的生物活性。我们设计了20个同源肽（约20个氨基酸长度），17个可溶性肽用于细胞附着试验。13个肽促进不同细胞形态的细胞粘附活性。肝素可抑制细胞对肽G1 EF 1、G1 EF 2、G2 EF 1、G3 EF 4和G5 EF 4的附着，肽G1 EF 1、G1 EF 2和G2 EF 1特异性结合多配体过表达细胞。EDTA抑制细胞与肽G2 EF 3、G3 EF 1、G3 EF 3、G5 EF 1、G5 EF 3和G5 EF 5的附着。此外，细胞与肽G3 EF 3、G5 EF 1和G5 EF 5的附着被抗整联蛋白α2和β1抗体抑制，而细胞与肽G5 EF 3的附着仅被抗整联蛋白β1抗体抑制。肝素和EDTA均抑制细胞与肽G1 EF 4、G3 EF 4和G5 EF 4的附着，抗整联蛋白抗体不抑制细胞附着。活性肽序列比对表明，syndecan结合肽含有“碱性氨基酸（BAA）-Gly-BAA”基序在分子的中间，整合素结合肽含有“酸性氨基酸（AAA）"-Gly-BAA基序。核心转换肽分析表明，“BAA-Gly-BAA”基序是关键的结合syndecans和“AAA-Gly-BAA”基序有潜力识别整联蛋白。这些发现对于理解层粘连蛋白的链特异性生物活性和评估受体特异性结合机制是有用的。
Each laminin α chain (α1-α5 chains) has chain-specific diverse biological functions. The C-terminal globular domain of the α chain consists of five laminin-like globular (LG1-5) modules and plays a critical role in biological activities. The LG modules consist of a 14-stranded β-sheet (A-N) 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-G4EF5). Here, we further analyze the biological activities of the E-F 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 α2 and β1 antibodies, whereas cell attachment to peptide G5EF3 was inhibited by only anti-integrin β1 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 "basic amino acid (BAA)-Gly-BAA" motif in the middle of the molecule and that the integrin-binding peptides contain an "acidic amino acid (AAA)"-Gly-BAA motif. Core-switched peptide analyses suggested that the "BAA-Gly-BAA" motif is critical for binding to syndecans and that the "AAA-Gly-BAA" 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.
层粘连蛋白 Alpha3 链 LG4 模块中生物活性环区域的环肽分析证明肽构象对生物活性的重要性
DOI：
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发表时间：
2007
期刊：
Biochemistry (印刷中)
影响因子：
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作者：
Kato-Takagaki;K.
通讯作者：
K.