3w9p

From Proteopedia

(Difference between revisions)

Revision as of 20:46, 3 August 2016

Crystal structure of monomeric FraC (second crystal form)

Structural highlights

3w9p is a 2 chain structure with sequence from Actfr. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	3lim, 3vwi
Gene:	FraC (ACTFR)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[ACTPC_ACTFR] Pore-forming protein that forms cations-selective hydrophilic pores of around 1 nm and causes cardiac stimulation and hemolysis. Pore formation is a multi-step process that involves specific recognition of membrane sphingomyelin (but neither cholesterol nor phosphatidylcholine) using aromatic rich region and adjacent phosphocholine (POC) binding site, firm binding to the membrane (mainly driven by hydrophobic interactions) accompanied by the transfer of the N-terminal region to the lipid-water interface and finally pore formation after oligomerization of several monomers.^[1]

Publication Abstract from PubMed

Pore-forming toxins (PFT) are water-soluble proteins that possess the remarkable ability to self-assemble on the membrane of target cells, where they form pores causing cell damage. Here, we elucidate the mechanism of action of the haemolytic protein fragaceatoxin C (FraC), a alpha-barrel PFT, by determining the crystal structures of FraC at four different stages of the lytic mechanism, namely the water-soluble state, the monomeric lipid-bound form, an assembly intermediate and the fully assembled transmembrane pore. The structure of the transmembrane pore exhibits a unique architecture composed of both protein and lipids, with some of the lipids lining the pore wall, acting as assembly cofactors. The pore also exhibits lateral fenestrations that expose the hydrophobic core of the membrane to the aqueous environment. The incorporation of lipids from the target membrane within the structure of the pore provides a membrane-specific trigger for the activation of a haemolytic toxin.

Structural basis for self-assembly of a cytolytic pore lined by protein and lipid.,Tanaka K, Caaveiro JM, Morante K, Gonzalez-Manas JM, Tsumoto K Nat Commun. 2015 Feb 26;6:6337. doi: 10.1038/ncomms7337. PMID:25716479^[2]

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

References

↑ Bellomio A, Morante K, Barlic A, Gutierrez-Aguirre I, Viguera AR, Gonzalez-Manas JM. Purification, cloning and characterization of fragaceatoxin C, a novel actinoporin from the sea anemone Actinia fragacea. Toxicon. 2009 Nov;54(6):869-80. doi: 10.1016/j.toxicon.2009.06.022. Epub 2009 Jun, 27. PMID:19563820 doi:10.1016/j.toxicon.2009.06.022
↑ Tanaka K, Caaveiro JM, Morante K, Gonzalez-Manas JM, Tsumoto K. Structural basis for self-assembly of a cytolytic pore lined by protein and lipid. Nat Commun. 2015 Feb 26;6:6337. doi: 10.1038/ncomms7337. PMID:25716479 doi:http://dx.doi.org/10.1038/ncomms7337

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/3w9p"

@@ Line 1: / Line 1: @@
 ==Crystal structure of monomeric FraC (second crystal form)==
 <StructureSection load='3w9p' size='340' side='right' caption='[[3w9p]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
@@ Line 5: / Line 6: @@
 </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3lim|3lim]], [[3vwi|3vwi]]</td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">FraC ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=396334 ACTFR])</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=3w9p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3w9p OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3w9p RCSB], [http://www.ebi.ac.uk/pdbsum/3w9p PDBsum]</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=3w9p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3w9p OCA], [http://pdbe.org/3w9p PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3w9p RCSB], [http://www.ebi.ac.uk/pdbsum/3w9p PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3w9p ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 11: / Line 12: @@
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
-Pore-forming toxins (PFTs) are proteins that are secreted as soluble molecules and are inserted into membranes to form oligomeric transmembrane pores. In this paper, we report the crystal structure of Fragaceatoxin C (FraC), a PFT isolated from the sea anemone Actinia fragacea, at 1.8 A resolution. It consists of a crown-shaped nonamer with an external diameter of about 11.0 nm and an internal diameter of approximately 5.0 nm. Cryoelectron microscopy studies of FraC in lipid bilayers reveal the pore structure that traverses the membrane. The shape and dimensions of the crystallographic oligomer are fully consistent with the membrane pore. The FraC structure provides insight into the interactions governing the assembly process and suggests the structural changes that allow for membrane insertion. We propose a nonameric pore model that spans the membrane by forming a lipid-free alpha-helical bundle pore.
+Pore-forming toxins (PFT) are water-soluble proteins that possess the remarkable ability to self-assemble on the membrane of target cells, where they form pores causing cell damage. Here, we elucidate the mechanism of action of the haemolytic protein fragaceatoxin C (FraC), a alpha-barrel PFT, by determining the crystal structures of FraC at four different stages of the lytic mechanism, namely the water-soluble state, the monomeric lipid-bound form, an assembly intermediate and the fully assembled transmembrane pore. The structure of the transmembrane pore exhibits a unique architecture composed of both protein and lipids, with some of the lipids lining the pore wall, acting as assembly cofactors. The pore also exhibits lateral fenestrations that expose the hydrophobic core of the membrane to the aqueous environment. The incorporation of lipids from the target membrane within the structure of the pore provides a membrane-specific trigger for the activation of a haemolytic toxin.
-Structural insights into the oligomerization and architecture of eukaryotic membrane pore-forming toxins.,Mechaly AE, Bellomio A, Gil-Carton D, Morante K, Valle M, Gonzalez-Manas JM, Guerin DM Structure. 2011 Feb 9;19(2):181-91. PMID:21300287<ref>PMID:21300287</ref>
+Structural basis for self-assembly of a cytolytic pore lined by protein and lipid.,Tanaka K, Caaveiro JM, Morante K, Gonzalez-Manas JM, Tsumoto K Nat Commun. 2015 Feb 26;6:6337. doi: 10.1038/ncomms7337. PMID:25716479<ref>PMID:25716479</ref>
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 3w9p" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

3w9p

From Proteopedia

Revision as of 20:46, 3 August 2016

Crystal structure of monomeric FraC (second crystal form)

Structural highlights

Function

Publication Abstract from PubMed

References

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