title: The topology of the C-terminal sections of the NCX1 Na (+) /Ca ( 2+) exchanger and the NCKX2 Na (+) /Ca ( 2+) -K (+) exchanger.
abstract: Mammalian Na (+) /Ca ( 2+) (NCX) and Na (+) /Ca ( 2+) -K (+) exchangers (NCKX) are polytopic membrane proteins that play critical roles in calcium homeostasis in many cells. Although hydropathy plots for NCX and NCKX are very similar, reported topological models for NCX1 and NCKX2 differ in the orientation of the three C-terminal transmembrane segments (TMS). NCX1 is thought to have 9 TMS and a re-entrant loop, whereas NCKX2 is thought to have 10 TMS. The current topological model of NCKX2 is very similar to the 10 membrane spanning helices seen in the recently reported crystal structure of NCX_MJ, a distantly related archaebacterial Na (+) /Ca ( 2+) exchanger. Here we reinvestigate the orientation of the three C-terminal TMS of NCX1 and NCKX2 using mass-tagging experiments of substituted cysteine residues. Our results suggest that NCX1, NCKX2 and NCX_MJ all share the same 10 TMS topology.
authors.affiliation: Department of Physiology and Pharmacology, Hotchkiss Brain Institute, Faculty of Medicine, University of Calgary, Calgary, AB, Canada.
authors.forename: Robert T
authors.initials: RT
authors.lastname: Szerencsei
authors.forename: Tashi G
authors.initials: TG
authors.lastname: Kinjo
authors.forename: Paul P M
authors.initials: PP
authors.lastname: Schnetkamp
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D002417:Cattle; D002460:Cell Line; D003545:Cysteine / Q000737:chemistry; D004285:Dogs; D006801:Humans; D007915:Lepidoptera; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D019831:Sodium-Calcium Exchanger / Q000737:chemistry* / Q000235:genetics
chemical_list: D019831:Sodium-Calcium Exchanger; C074530:potassium-dependent sodium-calcium exchanger; D003545:Cysteine
keywords: NCKX; NCX; Na/Ca exchanger; Na/Ca-K exchanger; SLC24; SLC8; calcium homeostasis; membrane proteins