5osh: Difference between revisions
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<StructureSection load='5osh' size='340' side='right' caption='[[5osh]], [[Resolution|resolution]] 4.30Å' scene=''> | <StructureSection load='5osh' size='340' side='right' caption='[[5osh]], [[Resolution|resolution]] 4.30Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5osh]] is a 12 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5OSH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5OSH FirstGlance]. <br> | <table><tr><td colspan='2'>[[5osh]] is a 12 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Legionella_pneumophila_subsp._pneumophila_570-co-h Legionella pneumophila subsp. pneumophila 570-co-h]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5OSH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5OSH FirstGlance]. <br> | ||
</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=5osh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5osh OCA], [http://pdbe.org/5osh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5osh RCSB], [http://www.ebi.ac.uk/pdbsum/5osh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5osh ProSAT]</span></td></tr> | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">VPS29, DC15, DC7, MDS007 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), VPS35, MEM3, TCCCTA00141 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), lp12_2303 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=933093 Legionella pneumophila subsp. pneumophila 570-CO-H])</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=5osh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5osh OCA], [http://pdbe.org/5osh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5osh RCSB], [http://www.ebi.ac.uk/pdbsum/5osh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5osh ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Disease == | == Disease == | ||
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== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/VPS29_HUMAN VPS29_HUMAN]] Essential component of the retromer complex, a complex required to retrieve lysosomal enzyme receptors (IGF2R and M6PR) from endosomes to the trans-Golgi network. Also required to regulate transcytosis of the polymeric immunoglobulin receptor (pIgR-pIgA). Has low protein phosphatase activity towards a serine-phosphorylated peptide derived from IGF2R (in vitro).<ref>PMID:15247922</ref> [[http://www.uniprot.org/uniprot/VPS35_HUMAN VPS35_HUMAN]] Essential component of the retromer complex, a complex required to retrieve lysosomal enzyme receptors (IGF2R and M6PR) from endosomes to the trans-Golgi network. Also required to regulate transcytosis of the polymeric immunoglobulin receptor (pIgR-pIgA).<ref>PMID:15247922</ref> | [[http://www.uniprot.org/uniprot/VPS29_HUMAN VPS29_HUMAN]] Essential component of the retromer complex, a complex required to retrieve lysosomal enzyme receptors (IGF2R and M6PR) from endosomes to the trans-Golgi network. Also required to regulate transcytosis of the polymeric immunoglobulin receptor (pIgR-pIgA). Has low protein phosphatase activity towards a serine-phosphorylated peptide derived from IGF2R (in vitro).<ref>PMID:15247922</ref> [[http://www.uniprot.org/uniprot/VPS35_HUMAN VPS35_HUMAN]] Essential component of the retromer complex, a complex required to retrieve lysosomal enzyme receptors (IGF2R and M6PR) from endosomes to the trans-Golgi network. Also required to regulate transcytosis of the polymeric immunoglobulin receptor (pIgR-pIgA).<ref>PMID:15247922</ref> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Microbial pathogens employ sophisticated virulence strategies to cause infections in humans. The intracellular pathogen Legionella pneumophila encodes RidL to hijack the host scaffold protein VPS29, a component of retromer and retriever complexes critical for endosomal cargo recycling. Here, we determined the crystal structure of L. pneumophila RidL in complex with the human VPS29-VPS35 retromer subcomplex. A hairpin loop protruding from RidL inserts into a conserved pocket on VPS29 that is also used by cellular ligands, such as Tre-2/Bub2/Cdc16 domain family member 5 (TBC1D5) and VPS9-ankyrin repeat protein for VPS29 binding. Consistent with the idea of molecular mimicry in protein interactions, RidL outcompeted TBC1D5 for binding to VPS29. Furthermore, the interaction of RidL with retromer did not interfere with retromer dimerization but was essential for association of RidL with retromer-coated vacuolar and tubular endosomes. Our work thus provides structural and mechanistic evidence into how RidL is targeted to endosomal membranes. | |||
Molecular mechanism for the subversion of the retromer coat by the Legionella effector RidL.,Romano-Moreno M, Rojas AL, Williamson CD, Gershlick DC, Lucas M, Isupov MN, Bonifacino JS, Machner MP, Hierro A Proc Natl Acad Sci U S A. 2017 Dec 11. pii: 1715361115. doi:, 10.1073/pnas.1715361115. PMID:29229824<ref>PMID:29229824</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 5osh" style="background-color:#fffaf0;"></div> | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Human]] | |||
[[Category: Legionella pneumophila subsp. pneumophila 570-co-h]] | |||
[[Category: Hierro, A]] | [[Category: Hierro, A]] | ||
[[Category: Isupov, M N]] | [[Category: Isupov, M N]] | ||
Revision as of 09:38, 20 December 2017
Legionella effectorLegionella effector
Structural highlights
Disease[VPS35_HUMAN] Defects in VPS35 are the cause of Parkinson disease type 17 (PARK17) [MIM:614203]. PARK17 is an autosomal dominant, adult-onset form of Parkinson disease. Parkinson disease is a complex neurodegenerative disorder characterized by bradykinesia, resting tremor, muscular rigidity and postural instability, as well as by a clinically significant response to treatment with levodopa. The pathology involves the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies (intraneuronal accumulations of aggregated proteins), in surviving neurons in various areas of the brain.[1] [2] [3] Function[VPS29_HUMAN] Essential component of the retromer complex, a complex required to retrieve lysosomal enzyme receptors (IGF2R and M6PR) from endosomes to the trans-Golgi network. Also required to regulate transcytosis of the polymeric immunoglobulin receptor (pIgR-pIgA). Has low protein phosphatase activity towards a serine-phosphorylated peptide derived from IGF2R (in vitro).[4] [VPS35_HUMAN] Essential component of the retromer complex, a complex required to retrieve lysosomal enzyme receptors (IGF2R and M6PR) from endosomes to the trans-Golgi network. Also required to regulate transcytosis of the polymeric immunoglobulin receptor (pIgR-pIgA).[5] Publication Abstract from PubMedMicrobial pathogens employ sophisticated virulence strategies to cause infections in humans. The intracellular pathogen Legionella pneumophila encodes RidL to hijack the host scaffold protein VPS29, a component of retromer and retriever complexes critical for endosomal cargo recycling. Here, we determined the crystal structure of L. pneumophila RidL in complex with the human VPS29-VPS35 retromer subcomplex. A hairpin loop protruding from RidL inserts into a conserved pocket on VPS29 that is also used by cellular ligands, such as Tre-2/Bub2/Cdc16 domain family member 5 (TBC1D5) and VPS9-ankyrin repeat protein for VPS29 binding. Consistent with the idea of molecular mimicry in protein interactions, RidL outcompeted TBC1D5 for binding to VPS29. Furthermore, the interaction of RidL with retromer did not interfere with retromer dimerization but was essential for association of RidL with retromer-coated vacuolar and tubular endosomes. Our work thus provides structural and mechanistic evidence into how RidL is targeted to endosomal membranes. Molecular mechanism for the subversion of the retromer coat by the Legionella effector RidL.,Romano-Moreno M, Rojas AL, Williamson CD, Gershlick DC, Lucas M, Isupov MN, Bonifacino JS, Machner MP, Hierro A Proc Natl Acad Sci U S A. 2017 Dec 11. pii: 1715361115. doi:, 10.1073/pnas.1715361115. PMID:29229824[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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