MD SIMULATIONS OF THE TRANSMEMBRANE REGION OF GOLGI GLYCOSYLTRANSFERASES

高尔基体糖基转移酶跨膜区的 MD 模拟

• 批准号: 2463834
• 负责人: P K QASBA
• 金额: --
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2463834
• 关键词: Golgi apparatus; computer simulation; enzyme structure; galactosyltransferases; membrane proteins; molecular dynamics; mutant; protein structure function

The beta-1,4-galactosyltransferase (beta-1,4GT) is a Golgi resident type II integral membrane protein, with a short cytoplasmic N-terminal domain, a transmembrane domain (TMD) and a large luminal C-terminal domain which is involved in the terminal glycosylation of secreted proteins. The TMD in this and in other similar Golgi resident proteins is largely hydrophobic in character and on the average shorter than the corresponding TMD in the plasma membrane type II proteins, and has been shown to be important for Golgi retention. However, the exact mechanism of its Golgi retention still remains unknown. The molecular dynamics (MD) simulation of the TMD of beta-1,4GT has been conducted to investigate whether its dynamic structural variations play any role in its Golgi retention. The starting structure of the TMD was assumed to be alpha-helical and the simulations were conducted in a periodic box of octonal molecules to account for the low dielectric membrane medium. Simulation of a double mutant in the TMD of beta-1,4GT (His->Leu, Cys->Ser), which shows lack of Golgi retention, was also conducted. Preliminary results show that the TMD of the wild type and double mutant have very similar dynamic behavior. A detailed MD simulations will aid in the understanding of the structural variations in TMD and the role it plays in Golgi retention.

β-1，4-半乳糖基转移酶（β-1，4GT）是高尔基体的居民 II型整合膜蛋白，具有短的胞质N-末端 结构域、跨膜结构域（TMD）和大管腔C-末端 结构域，其参与分泌的 proteins. 在这个和其他类似的高尔基体驻留蛋白质中的TMD 在很大程度上是疏水性的，并且平均来说短于 在质膜II型蛋白质中的相应TMD，并且已经被 对高尔基体的保留很重要。 但具体 其高尔基体保留的机制仍不清楚。 分子 对β-1，4涡轮增压器的TMD进行了动力学仿真 来研究它的动态结构变化 在高尔基体的保留。 战区导弹防御系统的初始结构是假定的 是α螺旋的，并且以周期性的方式进行模拟。 用于解释低介电膜的八元分子盒 介质 β-1，4 GT TMD双突变体的模拟 (His->Leu，Cys->Ser），其显示缺乏高尔基体保留， 进行。 初步结果显示，野生型和 双突变体具有非常相似的动力学行为。 详细的MD 模拟将有助于理解结构变化 在TMD中的作用及其在高尔基体保留中的作用。