IcmQ in the Type 4b Secretion System Contains an NAD+ Binding Domain

Jeremiah D. Farelli, James C. Gumbart, Ildikó V. Akey, Andrew Hempstead, Whitney Amyot, James F. Head, C. James McKnight, Ralph R. Isberg, Christopher W. Akey
2013 Structure  
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
more » ... 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.
doi:10.1016/j.str.2013.05.017 pmid:23850453 pmcid:PMC3816012 fatcat:uzrv3ecjobaetjnh6qrftiiw6a