title: Probing the structure and dynamics of caveolin-1 in a caveolae-mimicking asymmetric lipid bilayer model.
abstract: Caveolin-1 is the principle membrane protein of caveolae and plays an important role in various cellular processes. The protein contains two helices (H1 and H2) connected by a three-residue break. Although caveolin-1 is assumed to adopt a U-shaped conformation in the transmembrane domain, with both the N-terminus and C-terminus exposed to the cytoplasm, the structure and dynamics of caveolin-1 in membranes are still unclear. Here, we performed six molecular dynamics simulations to characterize the structure and dynamics of caveolin-1 (residues D82-S136; Cav182-136) in a caveolae-mimicking asymmetric lipid bilayer. The simulations reveal that the structure of the caveolin scaffolding domain of caveolin-1 is dynamic, as it could be either fully helical or partly unstructured. Cav182-136 inserts into the inner leaflet of the asymmetric lipid bilayer with a stable U-shaped conformation and orients almost vertical to the bilayer surface. The simulations also provide new insights into the effects of caveolin-1 on the morphology of caveolae and the possible interacting site of cholesterol on caveolin-1.
authors.affiliation: School of Pharmacy, East China University of Science and Technology, 130 Meilong Road, Shanghai, 200237, China.
authors.forename: Hanqi
authors.initials: H
authors.lastname: Liu
authors.affiliation: Drug Discovery and Design Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Science, 555 Zuchongzhi Road, Shanghai, 201203, China.
authors.forename: Linlin
authors.initials: L
authors.lastname: Yang
authors.affiliation: Drug Discovery and Design Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Science, 555 Zuchongzhi Road, Shanghai, 201203, China.
authors.forename: Qiansen
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, East China University of Science and Technology, 130 Meilong Road, Shanghai, 200237, China.
authors.forename: Lingxue
authors.initials: L
authors.lastname: Mao
authors.affiliation: School of Pharmacy, East China University of Science and Technology, 130 Meilong Road, Shanghai, 200237, China. hljiang@simm.ac.cn.|Drug Discovery and Design Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Science, 555 Zuchongzhi Road, Shanghai, 201203, China. hljiang@simm.ac.cn.
authors.forename: Hualiang
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Drug Discovery and Design Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Science, 555 Zuchongzhi Road, Shanghai, 201203, China. hyyang@simm.ac.cn.
authors.forename: Huaiyu
authors.initials: H
authors.lastname: Yang
mesh_terms: D051242:Caveolin 1 / Q000737:chemistry* / Q000378:metabolism*; D008051:Lipid Bilayers / Q000737:chemistry* / Q000378:metabolism*; D056004:Molecular Dynamics Simulation; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D017433:Protein Structure, Secondary
chemical_list: D051242:Caveolin 1; D008051:Lipid Bilayers; D010446:Peptide Fragments
keywords: Caveolae; Caveolin; Lipid raft; Molecular dynamics simulation