The discoidin domain receptors: collagen binding specificity and cooperation with integrins in cell adhesion / migration

盘状结构域受体：胶原蛋白结合特异性以及与细胞粘附/迁移中整合素的配合

• 批准号: G0701121/1
• 负责人: Birgit Leitinger
• 金额: $ 41.2万
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2008
• 资助国家: 英国
• 起止时间: 2008 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0701121%2F1
• 关键词: discoidin; domain; receptors; collagen; binding

We aim to study how cells use specialised proteins, called DDRs, to interact with collagen. When DDRs are faulty, they can cause disease. It is hoped that our work will benefit human health by creating reagents that may be useful in anti-DDR drug discovery programmes.The DDRs are novel drug targets for a number of human diseases, including arthritis and certain cancers. The DDRs recognise collagen, but we know very little about this interaction. When the DDRs bind collagen, they transmit a signal into the cell. We do not understand how the DDRs transmit such information. Collagen is the most abundant protein in our body and has a very complex structure. It is built like a rope, composed of three very long strands of amino acids that wind around each other. We will characterise the parts of collagen that are recognised by the DDRs. We will produce synthetic collagen fragments with the same rope-like structure as collagen and test which of these the DDRs use to transmit signals into cells. The DDRs are not the only proteins that interact with collagen. Another type of protein called integrin also binds collagen. Because the DDRs and integrins both recognise collagen, their relative contribution to biological function has been difficult to study. We have recently discovered that DDRs recognise a different part of collagen than integrins. We can thus make synthetic collagen fragments that will bind only DDRs, but not integrins, and use these to understand how the DDRs regulate the cell’s function.

我们的目标是研究细胞如何使用称为DDR的特殊蛋白质与胶原蛋白相互作用。当DDR出现故障时，它们可能会导致疾病。人们希望我们的工作将通过创造可能在抗DDR药物发现计划中有用的试剂来造福人类健康。DDR是许多人类疾病的新药物靶点，包括关节炎和某些癌症。DDR识别胶原蛋白，但我们对这种相互作用知之甚少。当DDR结合胶原蛋白时，它们将一个信号传递到细胞内。我们不了解复员方案如何传递这种信息。胶原蛋白是人体内含量最丰富的蛋白质，结构非常复杂。它的构造就像一根绳子，由三条相互缠绕的很长的氨基酸组成。我们将描述DDR识别的胶原蛋白部分的特征。我们将生产与胶原蛋白具有相同绳状结构的合成胶原蛋白片段，并测试DDR使用其中哪种胶原蛋白片段向细胞传递信号。DDR并不是唯一与胶原蛋白相互作用的蛋白质。另一种名为整合素的蛋白质也能结合胶原蛋白。由于DDRs和整合素都识别胶原蛋白，它们对生物功能的相对贡献一直很难研究。我们最近发现，DDR识别胶原的不同部分，而不是整合素。因此，我们可以制造出只与DDR结合，而不与整合素结合的合成胶原蛋白片段，并用这些片段来了解DDR如何调节细胞的功能。