5cqc

From Proteopedia

(Difference between revisions)

Revision as of 12:23, 14 June 2023

Crystal structure of the legionella pneumophila effector protein RavZ

Structural highlights

5cqc is a 1 chain structure with sequence from Legionella pneumophila. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

RAVZ_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]

Publication Abstract from PubMed

Autophagy is a conserved membrane transport pathway used to destroy pathogenic microbes that access the cytosol of cells. The intracellular pathogen Legionella pneumophila interferes with autophagy by delivering an effector protein, RavZ, into the host cytosol. RavZ acts by cleaving membrane-conjugated Atg8/LC3 proteins from pre-autophagosomal structures. Its remarkable efficiency allows minute quantities of RavZ to block autophagy throughout the cell. To understand how RavZ targets pre-autophagosomes and specifically acts only on membrane-associated Atg8 proteins, we elucidated its structure. Revealed is a catalytic domain related in fold to Ulp family deubiquitinase-like enzymes and a C-terminal PI3P-binding module. RavZ targets the autophagosome via the PI3P-binding module and a catalytic domain helix, and it preferentially binds high-curvature membranes, intimating localization to highly curved domains in autophagosome intermediate membranes. RavZ-membrane interactions enhance substrate affinity, providing a mechanism for interfacial activation that also may be used by host autophagy proteins engaging only lipidated Atg8 proteins.

The Legionella Anti-autophagy Effector RavZ Targets the Autophagosome via PI3P- and Curvature-Sensing Motifs.,Horenkamp FA, Kauffman KJ, Kohler LJ, Sherwood RK, Krueger KP, Shteyn V, Roy CR, Melia TJ, Reinisch KM Dev Cell. 2015 Sep 14;34(5):569-76. doi: 10.1016/j.devcel.2015.08.010. Epub 2015 , Sep 3. PMID:26343456^[12]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Choy A, Dancourt J, Mugo B, O'Connor TJ, Isberg RR, Melia TJ, Roy CR. The Legionella effector RavZ inhibits host autophagy through irreversible Atg8 deconjugation. Science. 2012 Nov 23;338(6110):1072-6. PMID:23112293 doi:10.1126/science.1227026
↑ Horenkamp FA, Kauffman KJ, Kohler LJ, Sherwood RK, Krueger KP, Shteyn V, Roy CR, Melia TJ, Reinisch KM. The Legionella Anti-autophagy Effector RavZ Targets the Autophagosome via PI3P- and Curvature-Sensing Motifs. Dev Cell. 2015 Sep 14;34(5):569-76. doi: 10.1016/j.devcel.2015.08.010. Epub 2015 , Sep 3. PMID:26343456 doi:http://dx.doi.org/10.1016/j.devcel.2015.08.010
↑ Yang A, Pantoom S, Wu YW. Elucidation of the anti-autophagy mechanism of the Legionella effector RavZ using semisynthetic LC3 proteins. Elife. 2017 Apr 11;6. pii: e23905. doi: 10.7554/eLife.23905. PMID:28395732 doi:http://dx.doi.org/10.7554/eLife.23905
↑ Kubori T, Bui XT, Hubber A, Nagai H. Legionella RavZ Plays a Role in Preventing Ubiquitin Recruitment to Bacteria-Containing Vacuoles. Front Cell Infect Microbiol. 2017 Aug 28;7:384. PMID:28971069 doi:10.3389/fcimb.2017.00384
↑ Kauffman KJ, Yu S, Jin J, Mugo B, Nguyen N, O'Brien A, Nag S, Lystad AH, Melia TJ. Delipidation of mammalian Atg8-family proteins by each of the four ATG4 proteases. Autophagy. 2018;14(6):992-1010. PMID:29458288 doi:10.1080/15548627.2018.1437341
↑ Park SW, Jeon P, Jun YW, Park JH, Lee SH, Lee S, Lee JA, Jang DJ. Monitoring LC3 RavZ-based probes. Sci Rep. 2019 Nov 12;9(1):16593. PMID:31719622 doi:10.1038/s41598-019-53372-2
↑ Park SW, Jun YW, Jeon P, Lee YK, Park JH, Lee SH, Lee JA, Jang DJ. LIR motifs and the membrane-targeting domain are complementary in the function of RavZ. BMB Rep. 2019 Dec;52(12):700-705. PMID:31722778 doi:10.5483/BMBRep.2019.52.12.211
↑ Omotade TO, Roy CR. Legionella pneumophila Excludes Autophagy Adaptors from the Ubiquitin-Labeled Vacuole in Which It Resides. Infect Immun. 2020 Jul 21;88(8):e00793-19. PMID:32482642 doi:10.1128/IAI.00793-19
↑ Yang A, Pantoom S, Wu YW. Distinct Mechanisms for Processing Autophagy Protein LC3-PE by RavZ and ATG4B. Chembiochem. 2020 Dec 1;21(23):3377-3382. PMID:32686895 doi:10.1002/cbic.202000359
↑ Park JH, Lee SH, Park SW, Jun YW, Kim K, Jeon P, Kim M, Lee JA, Jang DJ. Deciphering the role of a membrane-targeting domain in assisting endosomal and autophagic membrane localization of a RavZ protein catalytic domain. BMB Rep. 2021 Feb;54(2):118-123. PMID:33298241 doi:10.5483/BMBRep.2021.54.2.190
↑ Durgan J, Lystad AH, Sloan K, Carlsson SR, Wilson MI, Marcassa E, Ulferts R, Webster J, Lopez-Clavijo AF, Wakelam MJ, Beale R, Simonsen A, Oxley D, Florey O. Non-canonical autophagy drives alternative ATG8 conjugation to phosphatidylserine. Mol Cell. 2021 May 6;81(9):2031-2040.e8. PMID:33909989 doi:10.1016/j.molcel.2021.03.020
↑ Horenkamp FA, Kauffman KJ, Kohler LJ, Sherwood RK, Krueger KP, Shteyn V, Roy CR, Melia TJ, Reinisch KM. The Legionella Anti-autophagy Effector RavZ Targets the Autophagosome via PI3P- and Curvature-Sensing Motifs. Dev Cell. 2015 Sep 14;34(5):569-76. doi: 10.1016/j.devcel.2015.08.010. Epub 2015 , Sep 3. PMID:26343456 doi:http://dx.doi.org/10.1016/j.devcel.2015.08.010

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5cqc"

Categories: Large Structures | Legionella pneumophila | Horenkamp FA | Reinisch KM

@@ Line 1: / Line 1: @@
 ==Crystal structure of the legionella pneumophila effector protein RavZ==
-<StructureSection load='5cqc' size='340' side='right' caption='[[5cqc]], [[Resolution|resolution]] 2.98&Aring;' scene=''>
+<StructureSection load='5cqc' size='340' side='right'caption='[[5cqc]], [[Resolution|resolution]] 2.98&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5cqc]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Atcc_33152 Atcc 33152]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5CQC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5CQC FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5cqc]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Legionella_pneumophila Legionella pneumophila]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5CQC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5CQC FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BA:BARIUM+ION'>BA</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BA:BARIUM+ION'>BA</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">lpg1683 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=446 ATCC 33152])</td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5cqc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5cqc OCA], [https://pdbe.org/5cqc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5cqc RCSB], [https://www.ebi.ac.uk/pdbsum/5cqc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5cqc ProSAT]</span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5cqc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5cqc OCA], [http://pdbe.org/5cqc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5cqc RCSB], [http://www.ebi.ac.uk/pdbsum/5cqc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5cqc ProSAT]</span></td></tr>
 </table>
+== Function ==
+[https://www.uniprot.org/uniprot/RAVZ_LEGPH RAVZ_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).<ref>PMID:23112293</ref> <ref>PMID:26343456</ref> <ref>PMID:28395732</ref> <ref>PMID:28971069</ref> <ref>PMID:29458288</ref> <ref>PMID:31719622</ref> <ref>PMID:31722778</ref> <ref>PMID:32482642</ref> <ref>PMID:32686895</ref> <ref>PMID:33298241</ref> <ref>PMID:33909989</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 21: / Line 22: @@
 __TOC__
 </StructureSection>
-[[Category: Atcc 33152]]
+[[Category: Large Structures]]
-[[Category: Horenkamp, F A]]
+[[Category: Legionella pneumophila]]
-[[Category: Reinisch, K M]]
+[[Category: Horenkamp FA]]
-[[Category: Autophagy inhibitor]]
+[[Category: Reinisch KM]]
-[[Category: Hydrolase]]
-[[Category: Legionella pneumophila effector protein]]
-[[Category: Pi3p binding domain]]
-[[Category: Ulp-family cysteine protease]]

5cqc

From Proteopedia

Revision as of 12:23, 14 June 2023

Crystal structure of the legionella pneumophila effector protein RavZ

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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