Identification of alpha 1 beta 1 and alpha 2 beta 2 integrin recognition motifs within basement membrane ligands using phage display library screening, and their physiological effects on cells

使用噬菌体展示库筛选鉴定基底膜配体内的α1β1和α2β2整合素识别基序及其对细胞的生理作用

• 批准号: 5247330
• 负责人: Professor Dr. Johannes Andreas Eble
• 金额: --
• 依托单位: Institut für Physiologische Chemie und Pathobiochemie
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2000
• 资助国家: 德国
• 起止时间: 1999-12-31 至 2007-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5247330?language=en
• 关键词: Identification; alpha; beta; integrin; recognition

Integrins mediate contacts of cells with basal membrane components and other extracellular matrix (ECM) proteins, such as collagens and laminins. Among the collagen receptors, the two integrins a1ß1 and a2ß1 play a pivotal role in cell-matrix interaction. Recombinant soluble ectodomain heterodimers of a1ß1 and a2ß1 integrins help to identify the recognition motifs within their collagen and non-collagenous ligands, and allow to screen phage display libraries for conformationally restricted peptide sequences which imitate a1ß1 and a2ß1 integrin ligands. Characterization of such peptide mimetics for both collagen-binding integrins would disclose molecular details of collagen recognition, such as essential functional groups and structural requirements. Furthermore, these peptide agonists/antagonists will be useful tools in identifying the effects of integrin-collagen interaction on cell proliferation, adhesion, and migration, as well as gene expression of metallo-matrix-proteases (MMPs). MMPs degrade collagen and basal membrane proteins thus enabling tumor cells to penetrate through the basal membrane, causing tumor invasion and metastasis.

整联蛋白介导细胞与基底膜组分和其他细胞外基质（ECM）蛋白（如胶原蛋白和层粘连蛋白）的接触。在胶原受体中，两种整联蛋白α 1 β 1和α 2 β 1在细胞-基质相互作用中起关键作用。α 1 β 1和α 2 β 1整联蛋白的重组可溶性胞外域异源二聚体有助于鉴定其胶原和非胶原配体内的识别基序，并允许筛选噬菌体展示文库中模拟α 1 β 1和α 2 β 1整联蛋白配体的构象限制性肽序列。这两种胶原结合整联蛋白的肽模拟物的表征将揭示胶原识别的分子细节，如必需的官能团和结构要求。此外，这些肽激动剂/拮抗剂将是鉴定整合素-胶原相互作用对细胞增殖、粘附和迁移以及金属基质蛋白酶（MMPs）的基因表达的影响的有用工具。基质金属蛋白酶降解胶原和基底膜蛋白，从而使肿瘤细胞能够穿透基底膜，引起肿瘤侵袭和转移。