Evolution of a protein fold from toxin to physiological regulator: an endogenous potassium channel blocker in humans

钾通道阻断肽被海葵用作其毒液的有毒成分，也在包括人类在内的许多高等生物的蛋白质中发现。在大多数这些蛋白质中，这种毒素结构域的功能尚不清楚。该项目旨在确定人类蛋白质基质金属蛋白酶23中该结构域的结构和功能，该蛋白质在前列腺和其他癌症中可能起作用。我们的研究结果将不仅是感兴趣的跟踪这种毒素结构域的结构和功能的演变，但也将提供有价值的线索，它的作用在两个正常的生理功能的基质金属蛋白酶23，以及其潜在的病理作用在癌症中。

A potassium channel blocking peptide employed by sea anemones as a toxic component of their venom is also found in proteins from a number of higher organisms, including man. In most of these proteins the function of this toxin domain is unknown. This project aims to define the structure and function of this domain in a human protein, matrix metalloprotease 23, which has possible roles in prostate and other cancers. Our results will not only be of interest in tracing the structural and functional evolution of this toxin domain but will also provide valuable clues to its role in both the normal physiological function of matrix metalloprotease 23, as well as its potential pathological role in cancer.