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）是高尔基体驻留酶 II 型整合膜蛋白，具有短胞质 N 末端 结构域、跨膜结构域 (TMD) 和大的管腔 C 端 参与分泌的末端糖基化的结构域 蛋白质。 该蛋白和其他类似高尔基体驻留蛋白中的 TMD 具有很大的疏水性，平均比 质膜II型蛋白中相应的TMD，并且已被 表明对高尔基体保留很重要。 然而，确切的 其高尔基体滞留机制仍不清楚。 分子 已经对 beta-1,4GT 的 TMD 进行了动力学 (MD) 模拟 研究其动态结构变化是否发挥作用 在其高尔基体保留中。 假定 TMD 的起始结构 是α螺旋并且模拟是定期进行的 用于解释低介电膜的八元分子盒 中等的。 beta-1,4GT TMD 双突变体的模拟 （His->Leu，Cys->Ser），这表明缺乏高尔基体保留，也被 实施。 初步结果表明，野生型和 双突变体具有非常相似的动态行为。 详细MD 模拟将有助于理解结构变化 TMD 及其在高尔基体保留中的作用。