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1.C.12.1.1
Perfringolysin O, PFO.  Phosphatidylcholine in the outer leaflet increases the cholesterol concentration required to induce PFO binding while phosphatidylethanolamine and phosphatidylserine in the inner leaflet of asymmetric vesicles stabilized the formation of a deeply inserted conformation that does not form pores, even though it contains transmembrane segments (Lin and London 2014). This conformation may represent an important intermediate stage in PFO pore formation.  Cholesterol recognition, oligomerization, and the conformational changes involved in pore formation have been reviewed (Johnson and Heuck 2014), and the involvement of the D1 domain in structural transitions leading to pore formation has been studied (Kacprzyk-Stokowiec et al. 2014). Interaction of PFO with cholesterol is sufficient to initiate an irreversible sequence of coupled conformational changes that extend throughout the toxin molecule and induce pore formation (Heuck et al. 2007).  Once this transmembrane beta-barrel protein is inserted, PFO assembles into pore-forming oligomers containing 30-50 PFO monomers. These form a pore of up to 300 Å, far exceeding the size of most other proteinaceous pores.  Decreasing the length of the β-strands causes the pore to shrink (Lin et al. 2015).

Accession Number:P0C2E9
Protein Name:Perfringolysin O PFO aka TACY aka PFOR aka PFOA aka CPE0163
Length:500
Molecular Weight:55830.00
Species:Clostridium perfringens [1502]
Number of TMSs:1
Location1 / Topology2 / Orientation3: Secreted1
Substrate large molecules, small molecules

Cross database links:

HEGENOM: HBG337470
RefSeq: NP_561079.1   
Entrez Gene ID: 988404   
Pfam: PF01289   
BioCyc: CPER195102:CPE0163-MONOMER   
KEGG: cpe:CPE0163   

Gene Ontology

GO:0015485 F:cholesterol binding
GO:0019835 P:cytolysis
GO:0019836 P:hemolysis by symbiont of host erythrocytes
GO:0009405 P:pathogenesis

References (6)

[1] “An upstream regulatory sequence stimulates expression of the perfringolysin O gene of Clostridium perfringens.”  Shimizu T.et.al.   1987025
[2] “Complete genome sequence of Clostridium perfringens, an anaerobic flesh-eater.”  Shimizu T.et.al.   11792842
[3] “Cold-labile hemolysin produced by limited proteolysis of theta-toxin from Clostridium perfringens.”  Ohno-Iwashita Y.et.al.   2878682
[4] “Role of the essential thiol group in the thiol-activated cytolysin from Clostridium perfringens.”  Iwamoto M.et.al.   2888650
[5] “Crystallization and preliminary X-ray analysis of a thiol-activated cytolysin.”  Feil S.C.et.al.   8955365
[6] “Structure of a cholesterol-binding, thiol-activated cytolysin and a model of its membrane form.”  Rossjohn J.et.al.   9182756
Structure:
1M3I   1M3J   1PFO   2BK1   2BK2     

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FASTA formatted sequence
1:	MIRFKKTKLI ASIAMALCLF SQPVISFSKD ITDKNQSIDS GISSLSYNRN EVLASNGDKI 
61:	ESFVPKEGKK TGNKFIVVER QKRSLTTSPV DISIIDSVND RTYPGALQLA DKAFVENRPT 
121:	ILMVKRKPIN INIDLPGLKG ENSIKVDDPT YGKVSGAIDE LVSKWNEKYS STHTLPARTQ 
181:	YSESMVYSKS QISSALNVNA KVLENSLGVD FNAVANNEKK VMILAYKQIF YTVSADLPKN 
241:	PSDLFDDSVT FNDLKQKGVS NEAPPLMVSN VAYGRTIYVK LETTSSSKDV QAAFKALIKN 
301:	TDIKNSQQYK DIYENSSFTA VVLGGDAQEH NKVVTKDFDE IRKVIKDNAT FSTKNPAYPI 
361:	SYTSVFLKDN SVAAVHNKTD YIETTSTEYS KGKINLDHSG AYVAQFEVAW DEVSYDKEGN 
421:	EVLTHKTWDG NYQDKTAHYS TVIPLEANAR NIRIKARECT GLAWEWWRDV ISEYDVPLTN 
481:	NINVSIWGTT LYPGSSITYN