title: Structural basis for the counter-transport mechanism of a H+/Ca2+ exchanger.
abstract: Ca(2+)/cation antiporters catalyze the exchange of Ca(2+) with various cations across biological membranes to regulate cytosolic calcium levels. The recently reported structure of a prokaryotic Na(+)/Ca(2+) exchanger (NCX_Mj) revealed its overall architecture in an outward-facing state. Here, we report the crystal structure of a H(+)/Ca(2+) exchanger from Archaeoglobus fulgidus (CAX_Af) in the two representatives of the inward-facing conformation at 2.3 Å resolution. The structures suggested Ca(2+) or H(+) binds to the cation-binding site mutually exclusively. Structural comparison of CAX_Af with NCX_Mj revealed that the first and sixth transmembrane helices alternately create hydrophilic cavities on the intra- and extracellular sides. The structures and functional analyses provide insight into the mechanism of how the inward- to outward-facing state transition is triggered by the Ca(2+) and H(+) binding.
authors.affiliation: Department of Biophysics and Biochemistry, Graduate School of Science, University of Tokyo, 2-11-16 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Nishizawa
authors.forename: Satomi
authors.initials: S
authors.lastname: Kita
authors.forename: Andrés D
authors.initials: AD
authors.lastname: Maturana
authors.forename: Noritaka
authors.initials: N
authors.lastname: Furuya
authors.forename: Kunio
authors.initials: K
authors.lastname: Hirata
authors.forename: Go
authors.initials: G
authors.lastname: Kasuya
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ogasawara
authors.forename: Naoshi
authors.initials: N
authors.lastname: Dohmae
authors.forename: Takahiro
authors.initials: T
authors.lastname: Iwamoto
authors.forename: Ryuichiro
authors.initials: R
authors.lastname: Ishitani
authors.forename: Osamu
authors.initials: O
authors.lastname: Nureki
mesh_terms: D017920:Antiporters / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D019843:Archaeal Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D019611:Archaeoglobus fulgidus / Q000378:metabolism*; D001665:Binding Sites; D002118:Calcium / Q000737:chemistry / Q000378:metabolism; D027682:Cation Transport Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D018360:Crystallography, X-Ray; D006859:Hydrogen / Q000737:chemistry / Q000378:metabolism; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary
chemical_list: D017920:Antiporters; D019843:Archaeal Proteins; D027682:Cation Transport Proteins; C027614:calcium-hydrogen antiporters; D006859:Hydrogen; D002118:Calcium