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-摩尔乳糖基转移酶（beta-1,4GT）是高尔基居民 II型积分膜蛋白，具有短细胞质N末端 域，跨膜结构域（TMD）和大型腔C末端 与分泌的末端糖基化有关的域 蛋白质。 在此和其他类似的高尔基居民蛋白中的TMD 在特征和平均较短的疏水性上比 质膜II型蛋白质中的相应TMD，已经是 证明对高尔基的保留很重要。 但是，确切的 高尔基保留的机制仍然未知。 分子 已经进行了β-1,4GT的TMD的动力学（MD）模拟 调查其动态结构变化是否起任何作用 在其高尔基保留率中。 假定TMD的起始结构 为α-螺旋，并在周期性地进行模拟 八元分子盒，以解释低介电膜 中等的。 在β-1,4GT的TMD中模拟双重突变体 （his-> leu，cys-> ser），表明缺乏高尔基 实施。 初步结果表明野生类型的TMD和 双重突变体具有非常相似的动态行为。 详细的医学博士 模拟将有助于理解结构变化 在TMD及其在高尔基体保留中的作用。