title: Structure of the archaeal Na+/H+ antiporter NhaP1 and functional role of transmembrane helix 1.
abstract: We have determined the structure of the archaeal sodium/proton antiporter NhaP1 at 7 Å resolution by electron crystallography of 2D crystals. NhaP1 is a dimer in the membrane, with 13 membrane-spanning α-helices per protomer, whereas the distantly related bacterial NhaA has 12. Dimer contacts in the two antiporters are very different, but the structure of a six-helix bundle at the tip of the protomer is conserved. The six-helix bundle of NhaA contains two partially unwound α-helices thought to harbour the ion-translocation site, which is thus similar in NhaP1. A model of NhaP1 based on detailed sequence comparison and the NhaA structure was fitted to the 7 Å map. The additional N-terminal helix 1 of NhaP1, which appears to be an uncleaved signal sequence, is located near the dimer interface. Similar sequences are present in many eukaryotic homologues of NhaP1, including NHE1. Although fully folded and able to dimerize, NhaP1 constructs without helix 1 are inactive. Possible reasons are investigated and discussed.
authors.affiliation: Department of Structural Biology, Max Planck Institute of Biophysics, Frankfurt am Main, Germany.
authors.forename: Panchali
authors.initials: P
authors.lastname: Goswami
authors.forename: Cristina
authors.initials: C
authors.lastname: Paulino
authors.forename: Dilem
authors.initials: D
authors.lastname: Hizlan
authors.forename: Janet
authors.initials: J
authors.lastname: Vonck
authors.forename: Ozkan
authors.initials: O
authors.lastname: Yildiz
authors.forename: Werner
authors.initials: W
authors.lastname: Kühlbrandt
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D003001:Cloning, Molecular; D017124:Conserved Sequence / Q000235:genetics; D003461:Crystallography; D017931:DNA Primers / Q000235:genetics; D019281:Dimerization; D017017:Methanococcus / Q000235:genetics*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000235:genetics*; D017433:Protein Structure, Secondary; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017923:Sodium-Hydrogen Exchangers / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure*; D013045:Species Specificity
chemical_list: D017931:DNA Primers; D017923:Sodium-Hydrogen Exchangers