Probing The Dynamics Of Caveolin-1 In A Caveolae Mimicking Asymmetric Lipid Bilayer Model

Caveolae are asymmetric lipid bilayer enriched in sphingolipids and cholesterol, which are involved in a number of biological processes, such as signal transduction, endocytosis and lipid trafficking. Caveolin is the principle component of caveolae. As dysfunction and misregulation of caveolin are linked to various diseases, it is of great importance to investigate caveolin. However, the structure of caveolin as well as its conformation in caveolae is still unclear. Among the three isoforms of caveolin, caveolin-1 is the most ubiquitous, which is also a cholesterol binding protein. In the present thesis, we investigated the structure and dynamic of caveolin-1 in a caveolae mimicking asymmetric lipid bilayer. In Chapter 2, an asymmetric lipid bilayer model was constructed to mimic the caveolae and we performed molecular dynamics (MD) simulation on the model. The system was stable during the MD simulation. On the basis of the MD simulation in Chapter 2, we constructed the complex system consisting of caveolin-1 (residues 82-136) and asymmetric lipid bilayer in Chapter 3. After two one-microsecond MD simulations, the caveolin scaffolding domain (CSD) of caveolin-1 (residues 82-101) turned out to be an extended part of Helix 1 and caveolin-1 (residues 82-136) adopted a stable "U"-shaped conformation in the asymmetric lipid bilayer. In the simulations, caveolin-1 (residues 82-136) only inserted in the inner leaflet. And caveolin-1 increased the order of the phospholipids in the inner leaflet while it decreased the order of the phospholipids in the outer leaflet. Besides, no preferential binding site of cholesterol was observed on CSD.