title: Determinants of pore folding in potassium channel biogenesis.
abstract: Many ion channels, both selective and nonselective, have reentrant pore loops that contribute to the architecture of the permeation pathway. It is a fundamental feature of these diverse channels, regardless of whether they are gated by changes of membrane potential or by neurotransmitters, and is critical to function of the channel. Misfolding of the pore loop leads to loss of trafficking and expression of these channels on the cell surface. Mature tetrameric potassium channels contain an α-helix within the pore loop. We systematically mutated the "pore helix" residues of the channel Kv1.3 and assessed the ability of the monomer to fold into a tertiary reentrant loop. Our results show that pore loop residues form a canonical α-helix in the monomer early in biogenesis and that disruption of tertiary folding is caused by hydrophilic substitutions only along one face of this α-helix. These results provide insight into the determinants of the reentrant pore conformation, which is essential for ion channel function.
authors.affiliation: Department of Physiology, University of Pennsylvania, Philadelphia, PA 19104-6085.
authors.forename: Erin
authors.initials: E
authors.lastname: Delaney
authors.forename: Pooja
authors.initials: P
authors.lastname: Khanna
authors.forename: LiWei
authors.initials: L
authors.lastname: Tu
authors.forename: John M
authors.initials: JM
authors.lastname: Robinson
authors.forename: Carol
authors.initials: C
authors.lastname: Deutsch
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015221:Potassium Channels / Q000096:biosynthesis* / Q000737:chemistry; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid
chemical_list: D015221:Potassium Channels
keywords: accessibility assay; cysteine scan; formation of Kv pore; glutamate scan