4o32: Difference between revisions

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== Function ==
== Function ==
[https://www.uniprot.org/uniprot/THIO2_PLAF7 THIO2_PLAF7] Participates in various redox reactions through the reversible oxidation of its active center dithiol to a disulfide and catalyzes dithiol-disulfide exchange reactions (PubMed:16910770, PubMed:22355694). As part of the translocon PTEX complex, plays a role in the export of parasite proteins into the host erythrocyte (By similarity). The translocon PTEX complex is a multi-protein machinery resident in the parasite parasitophorous vacuolar membrane, responsible for protein secretion into host cells (PubMed:19536257). May contribute to the unfolding of proteins containing the PEXEL localization motif before their passage through the translocon or regulate the PTEX complex function (PubMed:19536257).[UniProtKB:A0A509AQW5]<ref>PMID:16910770</ref> <ref>PMID:19536257</ref> <ref>PMID:22355694</ref> <ref>PMID:19536257</ref>  
[https://www.uniprot.org/uniprot/THIO2_PLAF7 THIO2_PLAF7] Participates in various redox reactions through the reversible oxidation of its active center dithiol to a disulfide and catalyzes dithiol-disulfide exchange reactions (PubMed:16910770, PubMed:22355694). As part of the translocon PTEX complex, plays a role in the export of parasite proteins into the host erythrocyte (By similarity). The translocon PTEX complex is a multi-protein machinery resident in the parasite parasitophorous vacuolar membrane, responsible for protein secretion into host cells (PubMed:19536257). May contribute to the unfolding of proteins containing the PEXEL localization motif before their passage through the translocon or regulate the PTEX complex function (PubMed:19536257).[UniProtKB:A0A509AQW5]<ref>PMID:16910770</ref> <ref>PMID:19536257</ref> <ref>PMID:22355694</ref> <ref>PMID:19536257</ref>  
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== Publication Abstract from PubMed ==
Survival of the malaria parasite Plasmodium falciparum when it infects red blood cells depends upon its ability to export hundreds of its proteins beyond an encasing vacuole. Protein export is mediated by a parasite-derived protein complex, the Plasmodium translocon of exported proteins (PTEX), and requires unfolding of the different cargos prior to their translocation across the vacuolar membrane. Unfolding is performed by the AAA+protein unfoldase HSP101/ClpB2 and the thioredoxin-2 enzyme (TRX2). Protein trafficking is dramatically impaired in parasites with defective HSP101 or lacking TRX2. These two PTEX subunits drive export and are targets for the design of a novel class of antimalarials: protein export inhibitors. To rationalize inhibitor design, we solved the crystal structure of Pfal-TRX2 at 2.2-A resolution. Within the asymmetric unit, the three different copies of this protein disulfide reductase sample its two redox catalytic states. Size exclusion chromatography and small-angle X-ray scattering (SAXS) analyses demonstrate that Pfal-TRX2 is monomeric in solution. A non-conserved N-terminal extension precedes the canonical thioredoxin-fold; although it is not observed in our structure, our solution analysis suggests it is flexible in contrast to Plasmodium thioredoxin-1. This represents a first step towards the reconstitution of the entire PTEX for mechanistic and structural studies.
Crystal structure and solution characterization of the thioredoxin-2 from Plasmodium falciparum, a constituent of an essential parasitic protein export complex.,Peng M, Cascio D, Egea PF Biochem Biophys Res Commun. 2014 Dec 2. pii: S0006-291X(14)02137-8. doi:, 10.1016/j.bbrc.2014.11.096. PMID:25475729<ref>PMID:25475729</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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==See Also==
==See Also==

Revision as of 17:07, 13 March 2024

Structure of a malarial proteinStructure of a malarial protein

Structural highlights

4o32 is a 3 chain structure with sequence from Plasmodium falciparum 3D7. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.196Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

THIO2_PLAF7 Participates in various redox reactions through the reversible oxidation of its active center dithiol to a disulfide and catalyzes dithiol-disulfide exchange reactions (PubMed:16910770, PubMed:22355694). As part of the translocon PTEX complex, plays a role in the export of parasite proteins into the host erythrocyte (By similarity). The translocon PTEX complex is a multi-protein machinery resident in the parasite parasitophorous vacuolar membrane, responsible for protein secretion into host cells (PubMed:19536257). May contribute to the unfolding of proteins containing the PEXEL localization motif before their passage through the translocon or regulate the PTEX complex function (PubMed:19536257).[UniProtKB:A0A509AQW5][1] [2] [3] [4]

See Also

References

  1. ↑ Nickel C, Rahlfs S, Deponte M, Koncarevic S, Becker K. Thioredoxin networks in the malarial parasite Plasmodium falciparum. Antioxid Redox Signal. 2006 Jul-Aug;8(7-8):1227-39. doi: 10.1089/ars.2006.8.1227. PMID:16910770 doi:http://dx.doi.org/10.1089/ars.2006.8.1227
  2. ↑ de Koning-Ward TF, Gilson PR, Boddey JA, Rug M, Smith BJ, Papenfuss AT, Sanders PR, Lundie RJ, Maier AG, Cowman AF, Crabb BS. A newly discovered protein export machine in malaria parasites. Nature. 2009 Jun 18;459(7249):945-9. doi: 10.1038/nature08104. PMID:19536257 doi:http://dx.doi.org/10.1038/nature08104
  3. ↑ Sharma A, Sharma A, Dixit S, Sharma A. Structural insights into thioredoxin-2: a component of malaria parasite protein secretion machinery. Sci Rep. 2011;1:179. doi: 10.1038/srep00179. Epub 2011 Dec 1. PMID:22355694 doi:http://dx.doi.org/10.1038/srep00179
  4. ↑ de Koning-Ward TF, Gilson PR, Boddey JA, Rug M, Smith BJ, Papenfuss AT, Sanders PR, Lundie RJ, Maier AG, Cowman AF, Crabb BS. A newly discovered protein export machine in malaria parasites. Nature. 2009 Jun 18;459(7249):945-9. doi: 10.1038/nature08104. PMID:19536257 doi:http://dx.doi.org/10.1038/nature08104

4o32, resolution 2.20Å

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