7DN9

Crystal structure of Salmonella effector in complex with NAD and host co-factor ARF1

Summary for 7DN9

• Entry DOI: 10.2210/pdb7dn9/pdb
• Descriptor: Putative cytoplasmic protein, ADP-ribosylation factor 1, NICOTINAMIDE-ADENINE-DINUCLEOTIDE, ... (5 entities in total)
• Functional Keywords: adp-ribosyltransferase, transferase
• Biological source: Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720); More
• Total number of polymer chains: 8
• Total formula weight: 222046.03

Authors

Ding, J.,Shao, F. (deposition date: 2020-12-09, release date: 2021-12-15, Last modification date: 2024-05-29)

Primary citation

Xu, Y.,Cheng, S.,Zeng, H.,Zhou, P.,Ma, Y.,Li, L.,Liu, X.,Shao, F.,Ding, J.
ARF GTPases activate Salmonella effector SopF to ADP-ribosylate host V-ATPase and inhibit endomembrane damage-induced autophagy.
Nat.Struct.Mol.Biol., 29:67-77, 2022

PubMed Abstract: Selective 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.

PubMed: 35046574
DOI: 10.1038/s41594-021-00710-6

Experimental method

X-RAY DIFFRACTION (3.29 Å)