title: Folding and stability of the aquaglyceroporin GlpF: Implications for human aqua(glycero)porin diseases.
abstract: Aquaporins are highly selective polytopic transmembrane channel proteins that facilitate the permeation of water across cellular membranes in a large diversity of organisms. Defects in aquaporin function are associated with common diseases, such as nephrogenic diabetes insipidus, congenital cataract and certain types of cancer. In general, aquaporins have a highly conserved structure; from prokaryotes to humans. The conserved structure, together with structural dynamics and the structural framework for substrate selectivity is discussed. The folding pathway of aquaporins has been a topic of several studies in recent years. These studies revealed that a conserved protein structure can be reached by following different folding pathways. Based on the available data, we suggest a complex folding pathway for aquaporins, starting from the insertion of individual helices up to the formation of the tetrameric aquaporin structure. The consequences of some known mutations in human aquaporin-encoding genes, which most likely affect the folding and stability of human aquaporins, are discussed.
authors.affiliation: Department of Pharmacy and Biochemistry, Johannes Gutenberg-University Mainz, 55128 Mainz, Germany.
authors.forename: Noreen
authors.initials: N
authors.lastname: Klein
authors.affiliation: Department of Pharmacy and Biochemistry, Johannes Gutenberg-University Mainz, 55128 Mainz, Germany.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Neumann
authors.affiliation: Department of Chemistry, University of Manitoba, Winnipeg, Manitoba R3T 2N2, Canada.
authors.forename: Joe D
authors.initials: JD
authors.lastname: O'Neil
authors.affiliation: Department of Pharmacy and Biochemistry, Johannes Gutenberg-University Mainz, 55128 Mainz, Germany. Electronic address: Dirk.Schneider@uni-mainz.de.
authors.forename: Dirk
authors.initials: D
authors.lastname: Schneider
mesh_terms: D020816:Amino Acid Motifs; D020346:Aquaporins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D002386:Cataract / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D017124:Conserved Sequence; D018500:Diabetes Insipidus, Nephrogenic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004926:Escherichia coli / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018272:Porins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017510:Protein Folding; D055550:Protein Stability; D017433:Protein Structure, Secondary; D014867:Water / Q000378:metabolism
chemical_list: D020346:Aquaporins; D029968:Escherichia coli Proteins; D018272:Porins; D014867:Water; C078043:GlpF protein, E coli
keywords: Aquaporin; GlpF; Membrane protein; Protein activity; Protein folding