title: IcmQ in the Type 4b secretion system contains an NAD+ binding domain.
abstract: A Type 4b secretion system (T4bSS) is required for Legionella growth in alveolar macrophages. IcmQ associates with IcmR, binds to membranes, and has a critical role in the T4bSS. We have now solved a crystal structure of IcmR-IcmQ to further our understanding of this complex. This structure revealed an amphipathic four-helix bundle, formed by IcmR and the N-terminal domain of IcmQ, which is linked to a novel C-terminal domain of IcmQ (Qc) by a linker helix. The Qc domain has structural homology with ADP ribosyltransferase domains in certain bacterial toxins and binds NAD(+) with a dissociation constant in the physiological range. Structural homology and molecular dynamics were used to identify an extended NAD(+) binding site on Qc, and the resulting model was tested by mutagenesis and binding assays. Based on the data, we suggest that IcmR-IcmQ binds to membranes, where it may interact with, or perhaps modify, a protein in the T4bSS when NAD(+) is bound.
authors.affiliation: Department of Physiology and Biophysics, Boston University School of Medicine, 700 Albany Street, Boston, MA 02118-2526, USA.
authors.forename: Jeremiah D
authors.initials: JD
authors.lastname: Farelli
authors.forename: James C
authors.initials: JC
authors.lastname: Gumbart
authors.forename: Ildikó V
authors.initials: IV
authors.lastname: Akey
authors.forename: Andrew
authors.initials: A
authors.lastname: Hempstead
authors.forename: Whitney
authors.initials: W
authors.lastname: Amyot
authors.forename: James F
authors.initials: JF
authors.lastname: Head
authors.forename: C James
authors.initials: CJ
authors.lastname: McKnight
authors.forename: Ralph R
authors.initials: RR
authors.lastname: Isberg
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Akey
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry*; D058947:Bacterial Secretion Systems; D001665:Binding Sites; D018360:Crystallography, X-Ray; D006860:Hydrogen Bonding; D016952:Legionella pneumophila; D008051:Lipid Bilayers / Q000737:chemistry; D008958:Models, Molecular; D018832:Molecular Chaperones / Q000737:chemistry; D008969:Molecular Sequence Data; D009243:NAD / Q000737:chemistry*; D011485:Protein Binding; D017433:Protein Structure, Secondary
chemical_list: D001426:Bacterial Proteins; D058947:Bacterial Secretion Systems; C432955:ICMQ protein, Legionella pneumophila; C432954:IcmR protein, Legionella pneumophila; D008051:Lipid Bilayers; D018832:Molecular Chaperones; D009243:NAD