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| | ==Structure of CNAG_02591 from Cryptococcus neoformans== | | ==Structure of CNAG_02591 from Cryptococcus neoformans== |
| - | <StructureSection load='4p5n' size='340' side='right' caption='[[4p5n]], [[Resolution|resolution]] 1.49Å' scene=''> | + | <StructureSection load='4p5n' size='340' side='right'caption='[[4p5n]], [[Resolution|resolution]] 1.49Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4p5n]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Crynh Crynh]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4P5N OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4P5N FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4p5n]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Cryptococcus_neoformans_var._grubii_H99 Cryptococcus neoformans var. grubii H99]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4P5N OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4P5N FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CD:CADMIUM+ION'>CD</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CD:CADMIUM+ION'>CD</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CNAG_02591 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=235443 CRYNH])</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=4p5n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4p5n OCA], [https://pdbe.org/4p5n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4p5n RCSB], [https://www.ebi.ac.uk/pdbsum/4p5n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4p5n 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=4p5n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4p5n OCA], [http://pdbe.org/4p5n PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4p5n RCSB], [http://www.ebi.ac.uk/pdbsum/4p5n PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4p5n ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/J9VKY2_CRYNH J9VKY2_CRYNH] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Crynh]] | + | [[Category: Cryptococcus neoformans var. grubii H99]] |
| - | [[Category: Almo, S C]] | + | [[Category: Large Structures]] |
| - | [[Category: Casadevall, A]] | + | [[Category: Almo SC]] |
| - | [[Category: McClelland, E E]] | + | [[Category: Casadevall A]] |
| - | [[Category: Structural genomic]] | + | [[Category: McClelland EE]] |
| - | [[Category: Ramagopal, U A]] | + | [[Category: Ramagopal UA]] |
| - | [[Category: Toro, R]] | + | [[Category: Toro R]] |
| - | [[Category: Cnag_02591]]
| + | |
| - | [[Category: Cryptococcus neoforman]]
| + | |
| - | [[Category: Nysgrc]]
| + | |
| - | [[Category: PSI, Protein structure initiative]]
| + | |
| - | [[Category: Psi-biology]]
| + | |
| Structural highlights
Function
J9VKY2_CRYNH
Publication Abstract from PubMed
The pathogenic yeast Cryptococcus neoformans causes cryptococcosis, a life-threatening fungal disease. C. neoformans has multiple virulence mechanisms that are non-host specific, induce damage and interfere with immune clearance. Microarray analysis of C. neoformans strains serially passaged in mice associated a small gene (CNAG_02591) with virulence. This gene, hereafter identified as HVA1 (hypervirulence-associated protein 1), encodes a protein that has homologs of unknown function in plant and animal fungi, consistent with a conserved mechanism. Expression of HVA1 was negatively correlated with virulence and was reduced in vitro and in vivo in both mouse- and Galleria-passaged strains of C. neoformans. Phenotypic analysis in hva1Delta and hva1Delta+HVA1 strains revealed no significant differences in established virulence factors. Mice infected intravenously with the hva1Delta strain had higher fungal burden in the spleen and brain, but lower fungal burden in the lungs, and died faster than mice infected with H99W or the hva1Delta+HVA1 strain. Metabolomics analysis demonstrated a general increase in all amino acids measured in the disrupted strain and a block in the TCA cycle at isocitrate dehydrogenase, possibly due to alterations in the nicotinamide cofactor pool. Macrophage fungal burden experiments recapitulated the mouse hypervirulent phenotype of the hva1Delta strain only in the presence of exogenous NADPH. The crystal structure of the Hva1 protein was solved, and a comparison of structurally similar proteins correlated with the metabolomics data and potential interactions with NADPH. We report a new gene that modulates virulence through a mechanism associated with changes in fungal metabolism.
A Small Protein Associated with Fungal Energy Metabolism Affects the Virulence of Cryptococcus neoformans in Mammals.,McClelland EE, Ramagopal UA, Rivera J, Cox J, Nakouzi A, Prabu MM, Almo SC, Casadevall A PLoS Pathog. 2016 Sep 1;12(9):e1005849. doi: 10.1371/journal.ppat.1005849., eCollection 2016 Sep. PMID:27583447[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ McClelland EE, Ramagopal UA, Rivera J, Cox J, Nakouzi A, Prabu MM, Almo SC, Casadevall A. A Small Protein Associated with Fungal Energy Metabolism Affects the Virulence of Cryptococcus neoformans in Mammals. PLoS Pathog. 2016 Sep 1;12(9):e1005849. doi: 10.1371/journal.ppat.1005849., eCollection 2016 Sep. PMID:27583447 doi:http://dx.doi.org/10.1371/journal.ppat.1005849
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