小窝蛋白-1在不对称双层膜模型中的动力学行为研究
发布时间：2018-12-19 21:37
【摘要】：小窝是细胞膜上富含鞘脂类和胆固醇的不对称双层膜结构,广泛参与信号传导、胞吞作用、脂类运输等多种生物进程。小窝蛋白是小窝的基本组成蛋白,小窝蛋白的功能障碍和错误调节与很多重大疾病的发生相关,因此对小窝蛋白的研究具有重大意义。但是小窝蛋白的结构尚未被解析,其在小窝中的构象也不清楚。小窝蛋白-1是最早被发现也是分布最广的小窝蛋白亚型,同时也是一个胆固醇结合蛋白。本论文主要对小窝蛋白-1在不对称磷脂双分子膜中的动力学行为进行研究。为了模拟真实的小窝膜环境,论文第二章主要搭建了内外膜中磷脂成分不一样的双层膜模型,对该模型的分子动力学模拟证实了模型的稳定性。论文第三章在第二章的基础上搭建了小窝蛋白-1(残基82-136)和不对称双层膜模型的复合体系,通过两条1微秒的分子动力学模拟,我们发现小窝蛋白-1的脚手架区域(残基82-101)能与跨膜区的一部分(残基102-107)一起形成一个完整的a-螺旋结构,小窝蛋白-1(残基82-136)能以“U”形构象在膜中稳定存在。在模拟中,小窝蛋白-1(残基82-136)仅插入不对称双层膜的内膜,能够增加内膜磷脂分子的有序性而降低外膜磷脂分子的有序性。另外,在小窝蛋白-1的脚手架区域没有发现胆固醇的倾向性结合位点。
[Abstract]:Vesicles are asymmetric bilayer membrane structures rich in sphingolipids and cholesterol on the cell membrane. They are involved in many biological processes such as signal transduction endocytosis lipid transport and so on. Fossa protein is the basic protein of small nest. The dysfunction and misregulation of nest protein are related to the occurrence of many major diseases, so the study of nest protein is of great significance. However, the structure of fossa protein has not been elucidated and its conformation in the fossa is unclear. Fossa protein-1 is the earliest found and most widely distributed fossa protein subtype, and is also a cholesterol binding protein. In this paper, the kinetic behavior of fosin-1 in asymmetric phospholipid bilayer membrane was studied. In the second chapter, a bilayer membrane model with different phospholipid composition in the inner and outer membrane was built, and the stability of the model was verified by molecular dynamics simulation. In the third chapter, based on the second chapter, the complex system of small nest protein-1 (residue 82-136) and asymmetric bilayer membrane model is built, and the molecular dynamics simulation is carried out by two one-microsecond molecular models. We found that the scaffold region of fossa protein-1 (residue 82-101) can form a complete a-helix structure with a part of the transmembrane region (residue 102-107). Fossa protein-1 (residue 82-136) can exist stably in the membrane with "U" conformation. In the simulation, fosin-1 (residue 82-136) was inserted only into the inner membrane of the asymmetric bilayer membrane, which could increase the order of the membrane phospholipid molecule and decrease the order of the outer membrane phospholipid molecule. In addition, no cholesterol tendentiousness binding site was found in the scaffold area of fossa-1.
【学位授予单位】：华东理工大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：Q51
本文编号：2387501
[Abstract]:Vesicles are asymmetric bilayer membrane structures rich in sphingolipids and cholesterol on the cell membrane. They are involved in many biological processes such as signal transduction endocytosis lipid transport and so on. Fossa protein is the basic protein of small nest. The dysfunction and misregulation of nest protein are related to the occurrence of many major diseases, so the study of nest protein is of great significance. However, the structure of fossa protein has not been elucidated and its conformation in the fossa is unclear. Fossa protein-1 is the earliest found and most widely distributed fossa protein subtype, and is also a cholesterol binding protein. In this paper, the kinetic behavior of fosin-1 in asymmetric phospholipid bilayer membrane was studied. In the second chapter, a bilayer membrane model with different phospholipid composition in the inner and outer membrane was built, and the stability of the model was verified by molecular dynamics simulation. In the third chapter, based on the second chapter, the complex system of small nest protein-1 (residue 82-136) and asymmetric bilayer membrane model is built, and the molecular dynamics simulation is carried out by two one-microsecond molecular models. We found that the scaffold region of fossa protein-1 (residue 82-101) can form a complete a-helix structure with a part of the transmembrane region (residue 102-107). Fossa protein-1 (residue 82-136) can exist stably in the membrane with "U" conformation. In the simulation, fosin-1 (residue 82-136) was inserted only into the inner membrane of the asymmetric bilayer membrane, which could increase the order of the membrane phospholipid molecule and decrease the order of the outer membrane phospholipid molecule. In addition, no cholesterol tendentiousness binding site was found in the scaffold area of fossa-1.
【学位授予单位】：华东理工大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：Q51
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