5ms2

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of the Legionella pneumophila effector protein RavZ in complex with human LC3B

Structural highlights

5ms2 is a 2 chain structure with sequence from Homo sapiens and 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 2.47Å
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 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.

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
↑ 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

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5ms2"

@@ Line 3: / Line 3: @@
 <StructureSection load='5ms2' size='340' side='right'caption='[[5ms2]], [[Resolution|resolution]] 2.47&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5ms2]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Legph Legph]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MS2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5MS2 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5ms2]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [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=5MS2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5MS2 FirstGlance]. <br>
-</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]), MAP1LC3B, MAP1ALC3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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]] 2.47&#8491;</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=5ms2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ms2 OCA], [http://pdbe.org/5ms2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ms2 RCSB], [http://www.ebi.ac.uk/pdbsum/5ms2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ms2 ProSAT]</span></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=5ms2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ms2 OCA], [https://pdbe.org/5ms2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ms2 RCSB], [https://www.ebi.ac.uk/pdbsum/5ms2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ms2 ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/MLP3B_HUMAN MLP3B_HUMAN]] Involved in formation of autophagosomal vacuoles (autophagosomes).
+[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 20: / Line 20: @@
 ==See Also==
-*[[Microtubule-associated protein|Microtubule-associated protein]]
+*[[Microtubule-associated protein 3D structures|Microtubule-associated protein 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Legph]]
+[[Category: Legionella pneumophila subsp. pneumophila str. Philadelphia 1]]
-[[Category: Pantoom, S]]
+[[Category: Pantoom S]]
-[[Category: Vetter, I R]]
+[[Category: Vetter IR]]
-[[Category: Wu, Y W]]
+[[Category: Wu YW]]
-[[Category: Autophagy]]
-[[Category: Host-pathogen interaction]]
-[[Category: Hydrolase]]

5ms2

From Proteopedia

Current revision

Crystal structure of the Legionella pneumophila effector protein RavZ in complex with human LC3B

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox