title: Topologically Diverse Human Membrane Proteins Partition to Liquid-Disordered Domains in Phase-Separated Lipid Vesicles.
abstract: The integration of membrane proteins into "lipid raft" membrane domains influences many biochemical processes. The intrinsic structural properties of membrane proteins are thought to mediate their partitioning between membrane domains. However, whether membrane topology influences the targeting of proteins to rafts remains unclear. To address this question, we examined the domain preference of three putative raft-associated membrane proteins with widely different topologies: human caveolin-3, C99 (the 99 residue C-terminal domain of the amyloid precursor protein), and peripheral myelin protein 22. We find that each of these proteins are excluded from the ordered domains of giant unilamellar vesicles containing coexisting liquid-ordered and liquid-disordered phases. Thus, the intrinsic structural properties of these three topologically distinct disease-linked proteins are insufficient to confer affinity for synthetic raft-like domains.
authors: Department of Biochemistry, ‡Center for Structural Biology, §Department of Molecular Physiology and Biophysics, ∥Department of Cell and Developmental Biology, Vanderbilt University School of Medicine , Nashville, Tennessee 37240, United States.
authors: Jonathan P
authors: JP
authors: Schlebach
authors: Department of Biochemistry, ‡Center for Structural Biology, §Department of Molecular Physiology and Biophysics, ∥Department of Cell and Developmental Biology, Vanderbilt University School of Medicine , Nashville, Tennessee 37240, United States.
authors: Paul J
authors: PJ
authors: Barrett
authors: Department of Biochemistry, ‡Center for Structural Biology, §Department of Molecular Physiology and Biophysics, ∥Department of Cell and Developmental Biology, Vanderbilt University School of Medicine , Nashville, Tennessee 37240, United States.
authors: Charles A
authors: CA
authors: Day
authors: Department of Biochemistry, ‡Center for Structural Biology, §Department of Molecular Physiology and Biophysics, ∥Department of Cell and Developmental Biology, Vanderbilt University School of Medicine , Nashville, Tennessee 37240, United States.
authors: Ji Hun
authors: JH
authors: Kim
authors: Department of Biochemistry, ‡Center for Structural Biology, §Department of Molecular Physiology and Biophysics, ∥Department of Cell and Developmental Biology, Vanderbilt University School of Medicine , Nashville, Tennessee 37240, United States.
authors: Anne K
authors: AK
authors: Kenworthy
authors: Department of Biochemistry, ‡Center for Structural Biology, §Department of Molecular Physiology and Biophysics, ∥Department of Cell and Developmental Biology, Vanderbilt University School of Medicine , Nashville, Tennessee 37240, United States.
authors: Charles R
authors: CR
authors: Sanders
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D051244:Caveolin 3 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D002784:Cholesterol / Q000737:chemistry / Q000378:metabolism; D005456:Fluorescent Dyes / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D021962:Membrane Microdomains / Q000737:chemistry* / Q000378:metabolism; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D008958:Models, Molecular; D009185:Myelin Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D010713:Phosphatidylcholines / Q000737:chemistry / Q000378:metabolism; D010714:Phosphatidylethanolamines / Q000737:chemistry; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D012235:Rhodamines / Q000737:chemistry; D013109:Sphingomyelins / Q000737:chemistry / Q000378:metabolism; D053835:Unilamellar Liposomes
chemical_list: D016564:Amyloid beta-Protein Precursor; C417736:CAV3 protein, human; D051244:Caveolin 3; D005456:Fluorescent Dyes; D009185:Myelin Proteins; C053685:N-(lissamine rhodamine B sulfonyl)-1,2-dioleoylphosphatidylethanolamine; C073687:PMP22 protein, human; D010446:Peptide Fragments; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D011994:Recombinant Proteins; D012235:Rhodamines; D013109:Sphingomyelins; D053835:Unilamellar Liposomes; C543304:amyloid beta-protein precursor C-terminal fragment beta, human; D002784:Cholesterol; C028694:1-palmitoyl-2-oleoylphosphatidylcholine