title: Structural basis for the membrane association of ankyrinG via palmitoylation.
abstract: By clustering various ion channels and transporters, ankyrin-G (AnkG) configures the membrane-excitation platforms in neurons and cardiomyocytes. AnkG itself localizes to specific areas on the plasma membrane via s-palmitoylation of Cys. However, the structural mechanism by which AnkG anchors to the membrane is not understood. In this study, we solved the crystal structures of the reduced and oxidized forms of the AnkG s-palmitoylation domain and used multiple long-term coarse-grained molecular dynamics simulations to analyze their membrane association. Here we report that the membrane anchoring of AnkG was facilitated by s-palmitoylation, defining a stable binding interface on the lipid membrane, and that AnkG without s-palmitoylation also preferred to stay near the membrane but did not have a unique binding interface. This suggests that AnkG in the juxtamembrane region is primed to accept lipid modification at Cys, and once that happens AnkG constitutes a rigid structural base upon which a membrane-excitation platform can be assembled.
authors.affiliation: Integrative Physiology, Department of Physiology, Graduate School of Medicine, Osaka University, Suita, JAPAN.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Fujiwara
authors.affiliation: Systems Bioinformatics, Graduate School of Information Sciences, Tohoku University, Sendai, JAPAN.|Graduate School of Information Sciences, Hiroshima City University, Hiroshima, JAPAN.
authors.forename: Hiroko X
authors.initials: HX
authors.lastname: Kondo
authors.affiliation: Systems Bioinformatics, Graduate School of Information Sciences, Tohoku University, Sendai, JAPAN.|Systems Bioinformatics, Tohoku Medical Megabank Organization, Tohoku University, Sendai, JAPAN.|United Centers for Advanced Research and Translational Medicine, Graduate School of Medicine, Tohoku University, Sendai, JAPAN.
authors.forename: Matsuyuki
authors.initials: M
authors.lastname: Shirota
authors.affiliation: Integrative Physiology, Department of Physiology, Graduate School of Medicine, Osaka University, Suita, JAPAN.
authors.forename: Megumi
authors.initials: M
authors.lastname: Kobayashi
authors.affiliation: Supramolecular Crystallography, Research Center for Structural and Functional Proteomics, Institute for Protein Research, Osaka University, Suita, JAPAN.
authors.forename: Kohei
authors.initials: K
authors.lastname: Takeshita
authors.affiliation: Supramolecular Crystallography, Research Center for Structural and Functional Proteomics, Institute for Protein Research, Osaka University, Suita, JAPAN.|Graduate School of Frontier Biosciences, Osaka University, Suita, JAPAN.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nakagawa
authors.affiliation: Integrative Physiology, Department of Physiology, Graduate School of Medicine, Osaka University, Suita, JAPAN.|Graduate School of Frontier Biosciences, Osaka University, Suita, JAPAN.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Okamura
authors.affiliation: Systems Bioinformatics, Graduate School of Information Sciences, Tohoku University, Sendai, JAPAN.|Systems Bioinformatics, Tohoku Medical Megabank Organization, Tohoku University, Sendai, JAPAN.|Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
authors.forename: Kengo
authors.initials: K
authors.lastname: Kinoshita
mesh_terms: D000818:Animals; D017487:Ankyrins / Q000737:chemistry*; D001369:Axons / Q000378:metabolism; D002462:Cell Membrane / Q000737:chemistry; D002850:Chromatography, Gel; D018360:Crystallography, X-Ray; D003545:Cysteine / Q000737:chemistry; D006801:Humans; D008055:Lipids / Q000737:chemistry; D054878:Lipoylation / Q000502:physiology*; D056004:Molecular Dynamics Simulation; D009474:Neurons / Q000378:metabolism; D010084:Oxidation-Reduction; D010100:Oxygen / Q000737:chemistry; D000072417:Protein Domains; D055503:Protein Multimerization; D051381:Rats; D013049:Spectrin / Q000378:metabolism
chemical_list: C490613:ANK3 protein, human; C490614:Ank3 protein, rat; D017487:Ankyrins; D008055:Lipids; D013049:Spectrin; D003545:Cysteine; D010100:Oxygen