The discovery of SycO highlights a new function for type III secretion effector chaperones.
Bacterial injectisomes deliver effector proteins straight into the cytosol of eukaryotic cells (type III secretion, T3S). Many effectors are associated with a specific chaperone that remains inside the bacterium when the effector is delivered. The structure of such chaperones and the way they interact with their substrate is well characterized but their main function remains elusive. Here, we describe and characterize SycO, a new chaperone for the Yersinia effector kinase YopO. The chaperone-binding domain (CBD) within YopO coincides with the membrane localization domain (MLD) targeting YopO to the host cell membrane. The CBD/MLD causes intrabacterial YopO insolubility and the binding of SycO prevents this insolubility but not folding and activity of the kinase. Similarly, SycE masks the MLD of YopE and SycT covers an aggregation-prone domain of YopT, presumably corresponding to its MLD. Thus, SycO, SycE and most likely SycT mask, inside the bacterium, a domain needed for proper localization of their cognate effector in the host cell. We propose that covering an MLD might be an essential function of T3S effector chaperones.
Letzelter
Michel
M
Biozentrum der Universität Basel, Basel, Switzerland.
Sorg
Isabel
I
Mota
Luís Jaime
LJ
Meyer
Salome
S
Stalder
Jacqueline
J
Feldman
Mario
M
Kuhn
Marina
M
Callebaut
Isabelle
I
Cornelis
Guy R
GR
D001426:Bacterial Proteins / Q000378:metabolism*; D001692:Biological Transport; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000378:metabolism; D006801:Humans; D018832:Molecular Chaperones / Q000502:physiology*; D011485:Protein Binding; D017510:Protein Folding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D015534:Trans-Activators / Q000378:metabolism; D015008:Yersinia enterocolitica / Q000502:physiology*
D001426:Bacterial Proteins; D018832:Molecular Chaperones; C081269:SycE protein, Yersinia; D015534:Trans-Activators; C116117:YopT protein, Yersinia; C415206:YopO protein, Yersinia enterocolitica; D017346:Protein Serine-Threonine Kinases; D003546:Cysteine Endopeptidases