5oec: Difference between revisions
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<StructureSection load='5oec' size='340' side='right' caption='[[5oec]], [[Resolution|resolution]] 2.30Å' scene=''> | <StructureSection load='5oec' size='340' side='right' caption='[[5oec]], [[Resolution|resolution]] 2.30Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5oec]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5OEC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5OEC FirstGlance]. <br> | <table><tr><td colspan='2'>[[5oec]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_cholerae-suis"_smith_1894 "bacillus cholerae-suis" smith 1894] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5OEC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5OEC FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> | ||
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MLY:N-DIMETHYL-LYSINE'>MLY</scene></td></tr> | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MLY:N-DIMETHYL-LYSINE'>MLY</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4cym|4cym]], [[4mi7|4mi7]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4cym|4cym]], [[4mi7|4mi7]]</td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">gtgE, IN36_21720, IN69_16745, IN77_18825 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=28901 "Bacillus cholerae-suis" Smith 1894]), RAB32 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=5oec FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5oec OCA], [http://pdbe.org/5oec PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5oec RCSB], [http://www.ebi.ac.uk/pdbsum/5oec PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5oec 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=5oec FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5oec OCA], [http://pdbe.org/5oec PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5oec RCSB], [http://www.ebi.ac.uk/pdbsum/5oec PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5oec ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/RAB32_HUMAN RAB32_HUMAN]] Acts as an A-kinase anchoring protein by binding to the type II regulatory subunit of protein kinase A and anchoring it to the mitochondrion. Also involved in synchronization of mitochondrial fission. Plays a role in the maturation of phagosomes that engulf pathogens, such as S.aureus and M.tuberculosis.<ref>PMID:12186851</ref> <ref>PMID:21255211</ref> | [[http://www.uniprot.org/uniprot/RAB32_HUMAN RAB32_HUMAN]] Acts as an A-kinase anchoring protein by binding to the type II regulatory subunit of protein kinase A and anchoring it to the mitochondrion. Also involved in synchronization of mitochondrial fission. Plays a role in the maturation of phagosomes that engulf pathogens, such as S.aureus and M.tuberculosis.<ref>PMID:12186851</ref> <ref>PMID:21255211</ref> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Salmonella infections require the delivery of bacterial effectors into the host cell that alter the regulation of host defense mechanisms. The secreted cysteine protease GtgE from S. Typhimurium manipulates vesicular trafficking by modifying the Rab32 subfamily via cleaving the regulatory switch I region. Here we present a comprehensive biochemical, structural, and computational characterization of GtgE in complex with Rab32. Interestingly, GtgE solely processes the inactive GDP-bound GTPase. The crystal structure of the Rab32:GDP substrate in complex with the inactive mutant GtgEC45A reveals the molecular basis of substrate recognition. In combination with atomistic molecular dynamics simulations, the structural determinants for protein and activity-state specificity are identified. Mutations in a central interaction hub lead to loss of the strict GDP specificity. Our findings shed light on the sequence of host cell manipulation events during Salmonella infection and provide an explanation for the dependence on the co-secreted GTPase activating protein SopD2. | |||
The protease GtgE from Salmonella exclusively targets inactive Rab GTPases.,Wachtel R, Brauning B, Mader SL, Ecker F, Kaila VRI, Groll M, Itzen A Nat Commun. 2018 Jan 3;9(1):44. doi: 10.1038/s41467-017-02110-1. PMID:29298974<ref>PMID:29298974</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 5oec" style="background-color:#fffaf0;"></div> | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Bacillus cholerae-suis smith 1894]] | |||
[[Category: Human]] | |||
[[Category: Braeuning, B]] | [[Category: Braeuning, B]] | ||
[[Category: Ecker, F]] | [[Category: Ecker, F]] | ||
Revision as of 11:11, 17 January 2018
Human Rab32 (18-201):GDP in complex with Salmonella GtgE (21-214) C45A mutantHuman Rab32 (18-201):GDP in complex with Salmonella GtgE (21-214) C45A mutant
Structural highlights
Function[RAB32_HUMAN] Acts as an A-kinase anchoring protein by binding to the type II regulatory subunit of protein kinase A and anchoring it to the mitochondrion. Also involved in synchronization of mitochondrial fission. Plays a role in the maturation of phagosomes that engulf pathogens, such as S.aureus and M.tuberculosis.[1] [2] Publication Abstract from PubMedSalmonella infections require the delivery of bacterial effectors into the host cell that alter the regulation of host defense mechanisms. The secreted cysteine protease GtgE from S. Typhimurium manipulates vesicular trafficking by modifying the Rab32 subfamily via cleaving the regulatory switch I region. Here we present a comprehensive biochemical, structural, and computational characterization of GtgE in complex with Rab32. Interestingly, GtgE solely processes the inactive GDP-bound GTPase. The crystal structure of the Rab32:GDP substrate in complex with the inactive mutant GtgEC45A reveals the molecular basis of substrate recognition. In combination with atomistic molecular dynamics simulations, the structural determinants for protein and activity-state specificity are identified. Mutations in a central interaction hub lead to loss of the strict GDP specificity. Our findings shed light on the sequence of host cell manipulation events during Salmonella infection and provide an explanation for the dependence on the co-secreted GTPase activating protein SopD2. The protease GtgE from Salmonella exclusively targets inactive Rab GTPases.,Wachtel R, Brauning B, Mader SL, Ecker F, Kaila VRI, Groll M, Itzen A Nat Commun. 2018 Jan 3;9(1):44. doi: 10.1038/s41467-017-02110-1. PMID:29298974[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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