title: Cholesterol as a co-solvent and a ligand for membrane proteins.
abstract: As of mid 2013 a Medline search on "cholesterol" yielded over 200,000 hits, reflecting the prominence of this lipid in numerous aspects of animal cell biology and physiology under conditions of health and disease. Aberrations in cholesterol homeostasis underlie both a number of rare genetic disorders and contribute to common sporadic and complex disorders including heart disease, stroke, type II diabetes, and Alzheimer's disease. The corresponding author of this review and his lab stumbled only recently into the sprawling area of cholesterol research when they discovered that the amyloid precursor protein (APP) binds cholesterol, a topic covered by the Hans Neurath Award lecture at the 2013 Protein Society Meeting. Here, we first provide a brief overview of cholesterol-protein interactions and then offer our perspective on how and why binding of cholesterol to APP and its C99 domain (β-CTF) promotes the amyloidogenic pathway, which is closely related to the etiology of Alzheimer's disease.
authors.affiliation: Department of Biochemistry, Center for Structural Biology and Institute of Chemical Biology, Vanderbilt University School of Medicine, Nashville, Tennessee, 37232.
authors.forename: Yuanli
authors.initials: Y
authors.lastname: Song
authors.forename: Anne K
authors.initials: AK
authors.lastname: Kenworthy
authors.forename: Charles R
authors.initials: CR
authors.lastname: Sanders
mesh_terms: D000544:Alzheimer Disease / Q000209:etiology / Q000473:pathology; D016564:Amyloid beta-Protein Precursor / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D002784:Cholesterol / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary
chemical_list: D016564:Amyloid beta-Protein Precursor; D008024:Ligands; D008565:Membrane Proteins; D010446:Peptide Fragments; C543304:amyloid beta-protein precursor C-terminal fragment beta, human; D002784:Cholesterol
keywords: Alzheimer's disease; C99; CRAC; GPCRs; amyloid precursor protein; cholesterol; integral membrane proteins; receptor; β-CTF