Molecular mechanism of bacterial effector proteins antagonizing host antibacterial autophagy and a general mechanism of cell-selective autophagy

Classical autophagy of eukaryotic cells is an important signaling pathway for cells to achieve intracellular material recycling and reuse in auxotrophic conditions.

On January 19, 2022, the research group of Wang Dacheng/Ding Jingjue from the Institute of Biophysics, Chinese Academy of Sciences and Shao Feng's team from the Beisheng Institute published a paper entitled "ARF GTPases activate Salmonella effector SopF to ADP- " in " Nature Structural & Molecular Biology " ribosylate host V-ATPase and inhibit endomembrane damage-induced autophagy" research paper .

Using co-immunoprecipitation-mass spectrometry, the researchers first identified the Salmonella effector protein SopF specifically binding to a class of small G proteins ARF in host cells, and successfully resolved the SopF-ARF1 protein complex and its ternary complex with NAD ⁺ three-dimensional structure of objects

As a proton pump, V-ATPase is widely distributed on the membranes of a variety of acidified inner membrane organelles, and the working principle of host cell antibacterial heterophagy, suggesting that damage to these inner membrane organelles may also activate the V-ATPase-ATG16L1 pathway to initiate cells A variety of selective autophagy

This work reveals the structural basis for the bacterial effector protein SopF to antagonize the host heterophagy ADP-ribosyltransferase activity and the regulatory mechanism dependent on the host small G protein ARF, and further discovers that V-ATPase is independent of proton pump function, Identify the new function of cell non-canonical autophagy activated by endomembrane system damage, and confirm that the V-ATPase-ATG16L1 pathway is a conserved mechanism for initiating a variety of cell-selective autophagy, providing a new study for the maintenance and regulation of endomembrane homeostasis direction

Researcher Ding Jingsui from the Institute of Biophysics, Chinese Academy of Sciences and Professor Shao Feng from the Beisheng Institute are the co-corresponding authors of this article.

Molecular mechanism of bacterial effector protein SopF antagonizing host antibacterial autophagy

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(Contributed by Wang Dacheng/Ding Jingsui Research Group)