|
|
| Line 3: |
Line 3: |
| | <StructureSection load='3kwv' size='340' side='right'caption='[[3kwv]], [[Resolution|resolution]] 3.10Å' scene=''> | | <StructureSection load='3kwv' size='340' side='right'caption='[[3kwv]], [[Resolution|resolution]] 3.10Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3kwv]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/"bacillus_cereus_var._anthracis"_(cohn_1872)_smith_et_al._1946 "bacillus cereus var. anthracis" (cohn 1872) smith et al. 1946]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KWV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3KWV FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3kwv]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacillus_anthracis Bacillus anthracis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KWV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3KWV FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></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]] 3.101Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">pagA ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1392 "Bacillus cereus var. anthracis" (Cohn 1872) Smith et al. 1946]), lef ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1392 "Bacillus cereus var. anthracis" (Cohn 1872) Smith et al. 1946])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Hydrolase Hydrolase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.83 3.4.24.83] </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=3kwv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kwv OCA], [https://pdbe.org/3kwv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3kwv RCSB], [https://www.ebi.ac.uk/pdbsum/3kwv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3kwv 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=3kwv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kwv OCA], [https://pdbe.org/3kwv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3kwv RCSB], [https://www.ebi.ac.uk/pdbsum/3kwv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3kwv ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/PAG_BACAN PAG_BACAN]] One of the three proteins composing the anthrax toxin, the agent which infects many mammalian species and that may cause death. PA binds to a receptor (ATR) in sensitive eukaryotic cells, thereby facilitating the translocation of the enzymatic toxin components, edema factor and lethal factor, across the target cell membrane. PA associated with LF causes death when injected, PA associated with EF produces edema. PA induces immunity to infection with anthrax. [[https://www.uniprot.org/uniprot/LEF_BACAN LEF_BACAN]] One of the three proteins composing the anthrax toxin, the agent which infects many mammalian species and that may cause death. LF is the lethal factor that, when associated with PA, causes death. LF is not toxic by itself. It is a protease that cleaves the N-terminal of most dual specificity mitogen-activated protein kinase kinases (MAPKKs or MAP2Ks) (except for MAP2K5). Cleavage invariably occurs within the N-terminal proline-rich region preceding the kinase domain, thus disrupting a sequence involved in directing specific protein-protein interactions necessary for the assembly of signaling complexes. There may be other cytosolic targets of LF involved in cytotoxicity. The proteasome may mediate a toxic process initiated by LF in the cell cytosol involving degradation of unidentified molecules that are essential for macrophage homeostasis. This is an early step in LeTx intoxication, but it is downstream of the cleavage by LF of MEK1 or other putative substrates.<ref>PMID:9563949</ref> <ref>PMID:9703991</ref> <ref>PMID:10475971</ref> <ref>PMID:11104681</ref> <ref>PMID:10338520</ref>
| + | [https://www.uniprot.org/uniprot/PAG_BACAN PAG_BACAN] One of the three proteins composing the anthrax toxin, the agent which infects many mammalian species and that may cause death. PA binds to a receptor (ATR) in sensitive eukaryotic cells, thereby facilitating the translocation of the enzymatic toxin components, edema factor and lethal factor, across the target cell membrane. PA associated with LF causes death when injected, PA associated with EF produces edema. PA induces immunity to infection with anthrax. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 27: |
Line 26: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Hydrolase]] | |
| - | [[Category: Large Structures]] | |
| - | [[Category: Feld, G K]] | |
| - | [[Category: Kintzer, A F]] | |
| - | [[Category: Krantz, B A]] | |
| | [[Category: Bacillus anthracis]] | | [[Category: Bacillus anthracis]] |
| - | [[Category: Cleavage on pair of basic residue]] | + | [[Category: Large Structures]] |
| - | [[Category: Lethal factor]] | + | [[Category: Feld GK]] |
| - | [[Category: Lethal toxin]] | + | [[Category: Kintzer AF]] |
| - | [[Category: Metal-binding]] | + | [[Category: Krantz BA]] |
| - | [[Category: Metalloprotease]]
| + | |
| - | [[Category: Octamer]]
| + | |
| - | [[Category: Protease]]
| + | |
| - | [[Category: Protective antigen]]
| + | |
| - | [[Category: Protein translocation]]
| + | |
| - | [[Category: Protein transport]]
| + | |
| - | [[Category: Protein unfolding]]
| + | |
| - | [[Category: Secreted]]
| + | |
| - | [[Category: Toxin]]
| + | |
| - | [[Category: Toxin-protein transport complex]]
| + | |
| - | [[Category: Virulence]]
| + | |
| Structural highlights
Function
PAG_BACAN One of the three proteins composing the anthrax toxin, the agent which infects many mammalian species and that may cause death. PA binds to a receptor (ATR) in sensitive eukaryotic cells, thereby facilitating the translocation of the enzymatic toxin components, edema factor and lethal factor, across the target cell membrane. PA associated with LF causes death when injected, PA associated with EF produces edema. PA induces immunity to infection with anthrax.
Publication Abstract from PubMed
The protein transporter anthrax lethal toxin is composed of protective antigen (PA), a transmembrane translocase, and lethal factor (LF), a cytotoxic enzyme. After its assembly into holotoxin complexes, PA forms an oligomeric channel that unfolds LF and translocates it into the host cell. We report the crystal structure of the core of a lethal toxin complex to 3.1-A resolution; the structure contains a PA octamer bound to four LF PA-binding domains (LF(N)). The first alpha-helix and beta-strand of each LF(N) unfold and dock into a deep amphipathic cleft on the surface of the PA octamer, which we call the alpha clamp. The alpha clamp possesses nonspecific polypeptide binding activity and is functionally relevant to efficient holotoxin assembly, PA octamer formation, and LF unfolding and translocation. This structure provides insight into the mechanism of translocation-coupled protein unfolding.
Structural basis for the unfolding of anthrax lethal factor by protective antigen oligomers.,Feld GK, Thoren KL, Kintzer AF, Sterling HJ, Tang II, Greenberg SG, Williams ER, Krantz BA Nat Struct Mol Biol. 2010 Oct 31. PMID:21037566[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Feld GK, Thoren KL, Kintzer AF, Sterling HJ, Tang II, Greenberg SG, Williams ER, Krantz BA. Structural basis for the unfolding of anthrax lethal factor by protective antigen oligomers. Nat Struct Mol Biol. 2010 Oct 31. PMID:21037566 doi:10.1038/nsmb.1923
|
