Department of Molecular and Cell Biology, Boston University Henry M. Goldman School of Dental Medicine, Boston, Massachusetts 02118; Department of Biological Sciences, Universidad Andres Bello, Santiago, Chile.
J Biol Chem. 2018 Aug 17;293(33):12653-12662. doi: 10.1074/jbc.X118.004819.
Defects in protein glycosylation can have a dramatic impact on eukaryotic cells and is associated with mental and developmental pathologies in humans. The studies outlined below illustrate how a basic biochemical problem in the mechanisms of protein glycosylation, specifically substrate transporters of nucleotide sugars, including ATP and 3'-phosphoadenyl-5'-phosphosulfate (PAPS), in the membrane of the Golgi apparatus and endoplasmic reticulum, expanded into diverse biological systems from mammals, including humans, to yeast, roundworms, and protozoa. Using these diverse model systems allowed my colleagues and me to answer fundamental biological questions that enabled us to formulate far-reaching hypotheses and expanded our knowledge of human diseases caused by malfunctions in the metabolic processes involved.
蛋白质糖基化的缺陷会对真核细胞产生巨大影响,并与人类的精神和发育病理学有关。下面概述的研究说明了蛋白质糖基化机制中的一个基本生化问题,即核苷酸糖的底物转运蛋白,包括三磷酸腺苷 (ATP) 和 3'-磷酸腺苷-5'-磷酸硫酸酯 (PAPS),在高尔基体和内质网膜中的作用,如何从哺乳动物(包括人类)扩展到酵母、线虫和原生动物等多种生物系统。使用这些不同的模型系统,我的同事和我能够回答基本的生物学问题,使我们能够形成深远的假设,并扩展我们对代谢过程功能障碍导致的人类疾病的认识。