5ms5
From Proteopedia
Low-salt structure of RavZ LIR2-fused human LC3B
Structural highlights
FunctionRAVZ_LEGPH Cysteine protease effector that inhibits host cell autophagy by targeting lipid-conjugated ATG8 family proteins on pre-autophagosomal structures (PubMed:23112293, PubMed:29458288, PubMed:32686895, PubMed:31722778, PubMed:31719622, PubMed:33298241, PubMed:26343456, PubMed:28395732). Specifically hydrolyzes the amide bond between the C-terminal glycine residue and an adjacent aromatic residue in ATG8 proteins conjugated to phosphatidylethanolamine (PE), producing an ATG8 protein that cannot be reconjugated by host ATG7 and ATG3 (PubMed:23112293, PubMed:29458288, PubMed:32686895, PubMed:26343456, PubMed:28395732). Mechanistically, Ravz interacts with ATG8 proteins conjugated to PE via its LIR motifs, extracts them from the membrane of autophagosomes and integrates the PE part into its own lipid-binding site (PubMed:28395732). It then removes the lipid component of the ATG8 protein (PubMed:28395732). Also able to mediate delipidation of ATG8 proteins conjugated to phosphatidylserine (PS) during non-canonical autophagy (PubMed:33909989). Inhibits host ubiquitin recruitment to bacteria-containing vacuoles, suggesting that it is able to mediate delipidation of other proteins in addition to ATG8 proteins (PubMed:28971069). It is however not involved in the exclusion of autophagy adapters from bacteria-containing vacuoles decorated with ubiquitin (PubMed:32482642).[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] MLP3B_HUMAN Involved in formation of autophagosomal vacuoles (autophagosomes). Publication Abstract from PubMedAutophagy is a conserved cellular process involved in the elimination of proteins and organelles. It is also used to combat infection with pathogenic microbes. The intracellular pathogen Legionella pneumophila manipulates autophagy by delivering the effector protein RavZ to deconjugate Atg8/LC3 proteins coupled to phosphatidylethanolamine (PE) on autophagosomal membranes. To understand how RavZ recognizes and deconjugates LC3-PE, we prepared semisynthetic LC3 proteins and elucidated the structures of the RavZ:LC3 interaction. Semisynthetic LC3 proteins allowed the analysis of structure-function relationships. RavZ extracts LC3-PE from the membrane before deconjugation. RavZ initially recognizes the LC3 molecule on membranes via its N-terminal LC3-interacting region (LIR) motif. The RavZ alpha3 helix is involved in extraction of the PE moiety and docking of the acyl chains into the lipid-binding site of RavZ that is related in structure to that of the phospholipid transfer protein Sec14. Thus, Legionella has evolved a novel mechanism to specifically evade host autophagy. Elucidation of the anti-autophagy mechanism of the Legionella effector RavZ using semisynthetic LC3 proteins.,Yang A, Pantoom S, Wu YW Elife. 2017 Apr 11;6. pii: e23905. doi: 10.7554/eLife.23905. PMID:28395732[12] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. Loading citation details.. Citations No citations found See AlsoReferences
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