IcmQ in the Type 4b secretion system contains an NAD+ binding domain

Structure. 2013 Aug 6;21(8):1361-73. doi: 10.1016/j.str.2013.05.017. Epub 2013 Jul 11.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Bacterial Proteins / chemistry*
  • Bacterial Secretion Systems
  • Binding Sites
  • Crystallography, X-Ray
  • Hydrogen Bonding
  • Legionella pneumophila*
  • Lipid Bilayers / chemistry
  • Models, Molecular
  • Molecular Chaperones / chemistry
  • Molecular Sequence Data
  • NAD / chemistry*
  • Protein Binding
  • Protein Structure, Secondary

Substances

  • Bacterial Proteins
  • Bacterial Secretion Systems
  • ICMQ protein, Legionella pneumophila
  • IcmR protein, Legionella pneumophila
  • Lipid Bilayers
  • Molecular Chaperones
  • NAD

Associated data

  • PDB/4EYY