4wdc: Difference between revisions
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==High-resolution crystal structure of water-soluble FraC (mutation F16P)== | ==High-resolution crystal structure of water-soluble FraC (mutation F16P)== | ||
<StructureSection load='4wdc' size='340' side='right' caption='[[4wdc]], [[Resolution|resolution]] 1.29Å' scene=''> | <StructureSection load='4wdc' size='340' side='right'caption='[[4wdc]], [[Resolution|resolution]] 1.29Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4wdc]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4WDC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4WDC FirstGlance]. <br> | <table><tr><td colspan='2'>[[4wdc]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Actfr Actfr]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4WDC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4WDC FirstGlance]. <br> | ||
</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=4wdc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wdc OCA], [http://pdbe.org/4wdc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4wdc RCSB], [http://www.ebi.ac.uk/pdbsum/4wdc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4wdc ProSAT]</span></td></tr> | </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=4wdc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wdc OCA], [http://pdbe.org/4wdc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4wdc RCSB], [http://www.ebi.ac.uk/pdbsum/4wdc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4wdc ProSAT]</span></td></tr> | ||
</table> | </table> | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Actfr]] | |||
[[Category: Large Structures]] | |||
[[Category: Caaveiro, J M.M]] | [[Category: Caaveiro, J M.M]] | ||
[[Category: Morante, K]] | [[Category: Morante, K]] | ||
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[[Category: Pore forming toxin]] | [[Category: Pore forming toxin]] | ||
[[Category: Protein-lipid interaction]] | [[Category: Protein-lipid interaction]] | ||
[[Category: Toxin]] | |||
Revision as of 11:16, 23 May 2019
High-resolution crystal structure of water-soluble FraC (mutation F16P)High-resolution crystal structure of water-soluble FraC (mutation F16P)
Structural highlights
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 PubMedThe physicochemical landscape of the bilayer modulates membrane protein function. Actinoporins are a family of potent hemolytic proteins from sea anemones acting at the membrane level. This family of cytolysins preferentially binds to target membranes containing sphingomyelin (SM), where they form lytic pores giving rise to cell death. Although the cytolytic activity of the actinoporin fragaceatoxin C (FraC) is sensitive to vesicles made of various lipid compositions, it is far from clear how this toxin adjusts its mechanism of action to a broad range of physiochemical landscapes. Herein, we show that the conserved residue Phe16 of FraC is critical for pore formation in cholesterol-rich membranes such as those of red blood cells (RBC). The interaction of a panel of muteins of Phe16 with model membranes composed of raft-like lipid domains is inactivated in cholesterol-rich membranes, but not in cholesterol-depleted membranes. These results indicate that actinoporins recognize different membrane environments, resulting in a wider repertoire of susceptible target membranes (and preys) for sea anemones. In addition, this study has unveiled promising candidates for the development of protein-based biosensors highly sensitive to the concentration of cholesterol within the membrane. A Pore-Forming Toxin Requires a Specific Residue for its Activity in Membranes with Particular Physicochemical Properties.,Morante K, Caaveiro JM, Tanaka K, Gonzalez-Manas JM, Tsumoto K J Biol Chem. 2015 Mar 10. pii: jbc.M114.615211. PMID:25759390[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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