5x90
Structure of DotL(656-783)-IcmS-IcmW-LvgA derived from Legionella pneumophila
Structural highlights
FunctionICMS_LEGPH Component of the Dot/Icm type IVB secretion system (T4BSS), which is used to inject bacterial effector proteins into eukaryotic host cells (PubMed:15661013, PubMed:18069892, PubMed:17040490, PubMed:22694730, PubMed:32513920). Part of a subcomplex which recruits effector proteins and delivers them to the core transmembrane subcomplex (PubMed:23028312, PubMed:32513920). The IcmS/IcmW protein complex plays an important role in protein translocation by interacting with multiple Dot/Icm effector proteins to facilitate their translocation into host cells (PubMed:15661013, PubMed:18069892). Interaction promotes conformational changes in the effector protein, which may facilitate display of a C-terminal translocation signal (PubMed:18069892). May maintain the substrates in a translocation competent form (PubMed:23028312). Required for intracellular growth in host cells, replicative phagosome formation and phagosome trafficking (PubMed:11115108). IcmS is required for IcmW stability (PubMed:15661013, PubMed:29203674).[1] [2] [3] [4] [5] [6] [7] [8] Publication Abstract from PubMedMany bacteria, including Legionella pneumophila, rely on the type IV secretion system to translocate a repertoire of effector proteins into the hosts for their survival and growth. Type IV coupling protein (T4CP) is a hexameric ATPase that links translocating substrates to the transenvelope secretion conduit. Yet, how a large number of effector proteins are selectively recruited and processed by T4CPs remains enigmatic. DotL, the T4CP of L. pneumophila, contains an ATPase domain and a C-terminal extension whose function is unknown. Unlike T4CPs involved in plasmid DNA translocation, DotL appeared to function by forming a multiprotein complex with four other proteins. Here, we show that the C-terminal extension of DotL interacts with DotN, IcmS, IcmW and an additionally identified subunit LvgA, and that this pentameric assembly binds Legionella effector proteins. We determined the crystal structure of this assembly and built an architecture of the T4CP holocomplex by combining a homology model of the ATPase domain of DotL. The holocomplex is a hexamer of a bipartite structure composed of a membrane-proximal ATPase domain and a membrane-distal substrate-recognition assembly. The presented information demonstrates the architecture and functional dissection of the multiprotein T4CP complexes and provides important insights into their substrate recruitment and processing. Architecture of the type IV coupling protein complex of Legionella pneumophila.,Kwak MJ, Kim JD, Kim H, Kim C, Bowman JW, Kim S, Joo K, Lee J, Jin KS, Kim YG, Lee NK, Jung JU, Oh BH Nat Microbiol. 2017 Jul 17;2:17114. doi: 10.1038/nmicrobiol.2017.114. PMID:28714967[9] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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