5io3

From Proteopedia

(Difference between revisions)

Revision as of 14:03, 30 August 2023

Crystal structure of the legionella pneumophila effector protein RavZ - I422

Structural highlights

5io3 is a 1 chain structure with sequence from Legionella pneumophila subsp. pneumophila str. Philadelphia 1. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.74Å
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

Hosts utilize macroautophagy/autophagy to clear invading bacteria; however, bacteria have also developed a specific mechanism to survive by manipulating the host cell autophagy mechanism. One pathogen, Legionella pneumophila, can hinder host cell autophagy by using the specific effector protein RavZ that cleaves phosphatidylethanolamine-conjugated LC3 on the phagophore membrane. However, the detailed molecular mechanisms associated with the function of RavZ have hitherto remained unclear. Here, we report on the biochemical characteristics of the RavZ-LC3 interaction, the solution structure of the 1:2 complex between RavZ and LC3, and crystal structures of RavZ showing different conformations of the active site loop without LC3. Based on our biochemical, structural, and cell-based analyses of RavZ and LC3, both distant flexible N- and C-terminal regions containing LC3-interacting region (LIR) motifs are important for substrate recognition. These results suggest a novel mechanism of RavZ action on the phagophore membrane and lay the groundwork for understanding how bacterial pathogens can survive autophagy.

The 1:2 complex between RavZ and LC3 reveals a mechanism for deconjugation of LC3 on the phagophore membrane.,Kwon DH, Kim S, Jung YO, Roh KH, Kim L, Kim BW, Hong SB, Lee IY, Song JH, Lee WC, Choi EJ, Hwang KY, Song HK Autophagy. 2017 Jan 2;13(1):70-81. doi: 10.1080/15548627.2016.1243199. Epub 2016 , Oct 28. PMID:27791457^[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
↑ Kwon DH, Kim S, Jung YO, Roh KH, Kim L, Kim BW, Hong SB, Lee IY, Song JH, Lee WC, Choi EJ, Hwang KY, Song HK. The 1:2 complex between RavZ and LC3 reveals a mechanism for deconjugation of LC3 on the phagophore membrane. Autophagy. 2017 Jan 2;13(1):70-81. doi: 10.1080/15548627.2016.1243199. Epub 2016 , Oct 28. PMID:27791457 doi:http://dx.doi.org/10.1080/15548627.2016.1243199

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/5io3"

@@ Line 3: / Line 3: @@
 <StructureSection load='5io3' size='340' side='right'caption='[[5io3]], [[Resolution|resolution]] 2.74&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5io3]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Legph Legph]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5IO3 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5IO3 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5io3]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Legionella_pneumophila_subsp._pneumophila_str._Philadelphia_1 Legionella pneumophila subsp. pneumophila str. Philadelphia 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5IO3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5IO3 FirstGlance]. <br>
-</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5hzy|5hzy]]</td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.74&#8491;</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=272624 LEGPH])</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=5io3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5io3 OCA], [https://pdbe.org/5io3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5io3 RCSB], [https://www.ebi.ac.uk/pdbsum/5io3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5io3 ProSAT]</span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5io3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5io3 OCA], [http://pdbe.org/5io3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5io3 RCSB], [http://www.ebi.ac.uk/pdbsum/5io3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5io3 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 22: / Line 23: @@
 </StructureSection>
 [[Category: Large Structures]]
-[[Category: Legph]]
+[[Category: Legionella pneumophila subsp. pneumophila str. Philadelphia 1]]
-[[Category: Hong, S B]]
+[[Category: Hong SB]]
-[[Category: Kim, B W]]
+[[Category: Kim B-W]]
-[[Category: Kim, L]]
+[[Category: Kim L]]
-[[Category: Kwon, D H]]
+[[Category: Kwon DH]]
-[[Category: Song, H K]]
+[[Category: Song HK]]
-[[Category: Atg4b]]
-[[Category: Atg8]]
-[[Category: Autophagy]]
-[[Category: Deconjugating enzyme]]
-[[Category: Hydrolase]]
-[[Category: Protease]]

5io3

From Proteopedia

Revision as of 14:03, 30 August 2023

Crystal structure of the legionella pneumophila effector protein RavZ - I422

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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