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6psn

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Revision as of 04:35, 11 April 2020

Anthrax toxin protective antigen channels bound to lethal factor

6psn, resolution 4.60Å

Structural highlights

6psn is a 8 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Activity:	Hydrolase, with EC number 3.4.24.83
Experimental data:	Check to display Experimental Data
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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. [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.^[1] ^[2] ^[3] ^[4] ^[5]

Publication Abstract from PubMed

Following assembly, the anthrax protective antigen (PA) forms an oligomeric translocon that unfolds and translocates either its lethal factor (LF) or edema factor (EF) into the host cell. Here, we report the cryo-EM structures of heptameric PA channels with partially unfolded LF and EF at 4.6 and 3.1-A resolution, respectively. The first alpha helix and beta strand of LF and EF unfold and dock into a deep amphipathic cleft, called the alpha clamp, which resides at the interface of two PA monomers. The alpha-clamp-helix interactions exhibit structural plasticity when comparing the structures of lethal and edema toxins. EF undergoes a largescale conformational rearrangement when forming the complex with the channel. A critical loop in the PA binding interface is displaced for about 4 A, leading to the weakening of the binding interface prior to translocation. These structures provide key insights into the molecular mechanisms of translocation-coupled protein unfolding and translocation.

Atomic structures of anthrax toxin protective antigen channels bound to partially unfolded lethal and edema factors.,Hardenbrook NJ, Liu S, Zhou K, Ghosal K, Hong Zhou Z, Krantz BA Nat Commun. 2020 Feb 11;11(1):840. doi: 10.1038/s41467-020-14658-6. PMID:32047164^[6]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Duesbery NS, Webb CP, Leppla SH, Gordon VM, Klimpel KR, Copeland TD, Ahn NG, Oskarsson MK, Fukasawa K, Paull KD, Vande Woude GF. Proteolytic inactivation of MAP-kinase-kinase by anthrax lethal factor. Science. 1998 May 1;280(5364):734-7. PMID:9563949
↑ Vitale G, Pellizzari R, Recchi C, Napolitani G, Mock M, Montecucco C. Anthrax lethal factor cleaves the N-terminus of MAPKKs and induces tyrosine/threonine phosphorylation of MAPKs in cultured macrophages. Biochem Biophys Res Commun. 1998 Jul 30;248(3):706-11. PMID:9703991 doi:http://dx.doi.org/S0006-291X(98)99040-4
↑ Duesbery NS, Vande Woude GF. Anthrax lethal factor causes proteolytic inactivation of mitogen-activated protein kinase kinase. J Appl Microbiol. 1999 Aug;87(2):289-93. PMID:10475971
↑ Vitale G, Bernardi L, Napolitani G, Mock M, Montecucco C. Susceptibility of mitogen-activated protein kinase kinase family members to proteolysis by anthrax lethal factor. Biochem J. 2000 Dec 15;352 Pt 3:739-45. PMID:11104681
↑ Tang G, Leppla SH. Proteasome activity is required for anthrax lethal toxin to kill macrophages. Infect Immun. 1999 Jun;67(6):3055-60. PMID:10338520
↑ Hardenbrook NJ, Liu S, Zhou K, Ghosal K, Hong Zhou Z, Krantz BA. Atomic structures of anthrax toxin protective antigen channels bound to partially unfolded lethal and edema factors. Nat Commun. 2020 Feb 11;11(1):840. doi: 10.1038/s41467-020-14658-6. PMID:32047164 doi:http://dx.doi.org/10.1038/s41467-020-14658-6

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6psn"

@@ Line 3: / Line 3: @@
 <SX load='6psn' size='340' side='right' viewer='molstar' caption='[[6psn]], [[Resolution|resolution]] 4.60&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6psn]] is a 8 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6PSN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6PSN FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6psn]] is a 8 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6PSN OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6PSN FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr>
+</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'>[http://en.wikipedia.org/wiki/Hydrolase Hydrolase], with EC number [http://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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6psn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6psn OCA], [http://pdbe.org/6psn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6psn RCSB], [http://www.ebi.ac.uk/pdbsum/6psn PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6psn ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6psn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6psn OCA], [http://pdbe.org/6psn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6psn RCSB], [http://www.ebi.ac.uk/pdbsum/6psn PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6psn ProSAT]</span></td></tr>
 </table>
 == Function ==

6psn

From Proteopedia

Revision as of 04:35, 11 April 2020

Anthrax toxin protective antigen channels bound to lethal factor

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

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