Legionella effectors

Legionella effectors

1. Modulate lipid metabolism

   • RalF
     • Recruits and activates Arf1 which is a PI4K interacting partner
   • VipD
     • Contains phospholipase A motifs
   • LepB
     • Has kinase activity and produces PI(3,4)P2 from PI(3)P - PI(3,4)P2 is the substrate for SidF
   • SidF
     • Phosphatase - removes D3 phosphate from PI(3,4)P2 and PI(3,4,5)P3 - enrichment of PI(4)P on LCV to promote fusion with ER vesicles

2. Subvert endocytic system

   • AnkX
     • Phosphorylcholinates Rab35 (inhibit it) to prevent sorting of EE to PM
   • VipD
     • Phospholipase that hydrolyses PI(3)P to alter lipid composition of endosomal membranes and prevent fusion with LCV - requires Rab5 as a cofactor - ensures it only acts on endosomes
   • SidK
     • Inhibits v-ATPase to prevent acidification of LCV and inhibit fusion with lysosome
   • RidL
     • Localies to LCV membrane and inhibits retrograde trafficking by interacting with Vps29 (component of heteropentameric retromer)

3. Manipulate secretory pathway

   • RalF
     • Recruit and activate Arf1
   • SidM
     • Extracts Rab1 from GDI, acts as GEF for Rab1, and AMPylates on Y77 to trap it in active form
   • LidA
     • Binds Rab1 to bridge it with tether and ER-derived vesicle
   • LepB
     • Bacterial GAP for Rab1
   • Lem3
     • De-PCylates Rab1 to counter AnkX and inhibit its activity on the LCV
   • AnkX
     • PCylates Rab1 on Ser76to strongly inhibit secretion (Rab1 required for secretion of vesicles from TGN)
   • SidD
     • DeAMPylates Rab1 (counters SidM)

4. Co-opt ubiquitin network

   • SidC
     • E3-like ubiquitin ligase which recruits E1-E2 complex to ubiquitinate unknown substrates - required for LCV biogenesis
   • LubX
     • Expressed late in infection and ubiquitinates SidH for degradation to regulate it
   • SidE
     • Ubiquitinates Rab proteins - unknown why