7dn8
Crystal structure of Salmonella effector SopF in complex with ARF1Crystal structure of Salmonella effector SopF in complex with ARF1
Structural highlights
FunctionPublication Abstract from PubMedSelective autophagy helps eukaryotes to cope with endogenous dangers or foreign invaders; its initiation often involves membrane damage. By studying a Salmonella effector SopF, we recently identified the vacuolar ATPase (V-ATPase)-ATG16L1 axis that initiates bacteria-induced autophagy. Here we show that SopF is an ADP-ribosyltransferase specifically modifying Gln124 of ATP6V0C in V-ATPase. We identify GTP-bound ADP-ribosylation factor (ARF) GTPases as a cofactor required for SopF functioning. Crystal structures of SopF-ARF1 complexes not only reveal structural basis of SopF ADP-ribosyltransferase activity but also a unique effector-binding mode adopted by ARF GTPases. Further, the N terminus of ARF1, although dispensable for high-affinity binding to SopF, is critical for activating SopF to modify ATP6V0C. Moreover, lysosome or Golgi damage-induced autophagic LC3 activation is inhibited by SopF or Q124A mutation of ATP6V0C, thus also mediated by the V-ATPase-ATG16L1 axis. In this process, the V-ATPase functions to sense membrane damages, which can be uncoupled from its proton-pumping activity. ARF GTPases activate Salmonella effector SopF to ADP-ribosylate host V-ATPase and inhibit endomembrane damage-induced autophagy.,Xu Y, Cheng S, Zeng H, Zhou P, Ma Y, Li L, Liu X, Shao F, Ding J Nat Struct Mol Biol. 2022 Jan;29(1):67-77. doi: 10.1038/s41594-021-00710-6. Epub , 2022 Jan 19. PMID:35046574[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
|
| ||||||||||||||||||