Departamento Bioquímica de la Nutrición, Instituto Superior de Investigaciones Biológicas (CONICET-UNT), Tucumán, Argentina.
FEBS Lett. 2010 Feb 5;584(3):625-30. doi: 10.1016/j.febslet.2009.12.012. Epub 2009 Dec 13.
Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a multifunctional enzyme related with Huntington's, Parkinson's and Alzheimer's diseases. The ability of negatively charged membranes to induce a rapid formation of GAPDH amyloid fibrils has been demonstrated, but the mechanisms by which GAPDH reaches the fibrillar state remains unclear. In this report, we describe the structural changes undergone by GAPDH at physiological pH and temperature conditions right from its interaction with acidic membranes until the amyloid fibril is formed. According to our results, the GAPDH-membrane binding induces a beta-structuring process along with a loss of quaternary structure in the enzyme. In this way, experimental evidences on the initial steps of GAPDH amyloid fibrils formation pathway are provided.
甘油醛-3-磷酸脱氢酶（GAPDH）是一种与亨廷顿氏病、帕金森病和阿尔茨海默病有关的多功能酶。已经证明带负电荷的膜能够诱导 GAPDH 淀粉样纤维的快速形成，但是 GAPDH 达到纤维状态的机制尚不清楚。在本报告中，我们描述了 GAPDH 在生理 pH 和温度条件下从与酸性膜相互作用到形成淀粉样纤维的结构变化。根据我们的结果，GAPDH-膜结合诱导酶的β结构形成过程以及四级结构的丧失。通过这种方式，提供了 GAPDH 淀粉样纤维形成途径的初始步骤的实验证据。
