Investigation of a novel supramolecular organisation of the oligomeric mucins MUC5AC MUC5B and MUC2

点击翻译按钮获取中文摘要

A layer of mucus is a common means of protecting the delicate exposed epithelial surfaces of an organism against its environment and a range of biological, chemical and physical insults. We have discovered that the gel-like characteristics of mucus in saliva and now potentially in other mucus gels (e.g. the respiratory, gastrointestinal and reproductive tracts) are caused by calcium binding in the large structural glycoproteins (mucins). Our evidence shows that this involves protein parts of the mucin linking mucin molecules together. Therefore we will identify the part(s) of the mucin responsible for calcium-binding by testing different parts of the molecule prepared separately and also in fragments of mucin purified from saliva. The details of how it functions and where it occurs in the structure of the mucin will be determined. We will also investigate whether mucins can be modified to remove or inactivate their calcium binding properties. This calcium dependent cross-link activity that we have detected in mucin is newly discovered and it is a potentially important mechanism contributing to the function of this vital protective barrier. Furthermore, an improved understanding of the organisation of this barrier has important implications for treatment of common diseases involving mucus overproduction (e.g. asthma and cystic fibrosis) and improved strategies for the delivery to and across epithelial surfaces of pharmaceuticals and gene therapy agents.