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1.C.14.1.1
Cytohemolysin precursor, HlyA (Vibrio cholerae cytolysin, VCC) is a beta-barrel pore-forming toxin (beta-PFT). A cryo-electron microscopic study revealed low resolution structures for different functional forms (Dutta et al., 2009). Crystal structures of the soluble and transmembrane heptamer reveal common features among disparate pore-forming toxins (De and Olson, 2011). The toxin forms transmembrane heptameric β-barrel channels with two lectin activities on the β-prism and the β-trefoil (Rai et al. 2013).  A ring of tryptophan residues forms the narrowest constriction in the transmembrane channel reminiscent of the phenylalanine clamp identified in anthrax protective antigen (Krantz et al., 2005).  A single point mutation prevents membrane integration and pore formation (Paul and Chattopadhyay 2012).  The deletion of the pre-stem segment does not affect membrane binding and pre-pore oligomer formation, but it critically abrogates the functional pore-forming activity of VCC (Paul and Chattopadhyay 2013).  The membrane-bound monomer can not form pores (Rai and Chattopadhyay 2014).  VCC can be delivered to host cells via extracellular bacterial vesicles (Elluri et al. 2014).  Loops within the membrane-proximal region of VCC play critical roles in determining the functional interactions of the toxin with the membrane lipids that allow pore formation (Rai and Chattopadhyay 2015).  VCC may interfer with signalling in the target cell as well as form pores (Khilwani and Chattopadhyay 2015).  A functional map of the VCC membrane-binding surface has been published (De et al. 2015).  Residues involved in oligomerization have been identified (Rai and Chattopadhyay 2016).

Accession Number:P09545
Protein Name:HlyA aka VCA0219
Length:741
Molecular Weight:81962.00
Species:Vibrio cholerae [666]
Number of TMSs:1
Location1 / Topology2 / Orientation3: Secreted1 / Multi-pass membrane protein2
Substrate ions

Cross database links:

HEGENOM: HBG739831
RefSeq: NP_232618.1   
Entrez Gene ID: 2612877   
Pfam: PF12563    PF07968    PF00652   
KEGG: vch:VCA0219   

Gene Ontology

GO:0020002 C:host cell plasma membrane
GO:0016021 C:integral to membrane
GO:0005529 F:sugar binding
GO:0019835 P:cytolysis
GO:0019836 P:hemolysis by symbiont of host erythrocytes
GO:0009405 P:pathogenesis

References (5)

[1] “Extracellular proteins of Vibrio cholerae: nucleotide sequence of the structural gene (hlyA) for the haemolysin of the haemolytic El Tor strain O17 and characterization of the hlyA mutation in the non-haemolytic classical strain 569B.”  Alm R.A.et.al.   3050359
[2] “Nucleotide sequences and comparison of the hemolysin determinants of Vibrio cholerae El Tor RV79(Hly+) and RV79(Hly-) and classical 569B(Hly-).”  Rader A.E.et.al.   2453464
[3] “Two-step processing for activation of the cytolysin/hemolysin of Vibrio cholerae O1 biotype El Tor: nucleotide sequence of the structural gene (hlyA) and characterization of the processed products.”  Yamamoto K.et.al.   2174833
[4] “DNA sequence of both chromosomes of the cholera pathogen Vibrio cholerae.”  Heidelberg J.F.et.al.   10952301
[5] “Crystal structure of the Vibrio cholerae cytolysin (VCC) pro-toxin and its assembly into a heptameric transmembrane pore.”  Olson R.et.al.   15978620
Structure:
1XEZ   3o44     

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Predict TMSs (Predict number of transmembrane segments)
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FASTA formatted sequence
1:	MPKLNRCAIA IFTILSAISS PTLLANINEP SGEAADIISQ VADSHAIKYY NAADWQAEDN 
61:	ALPSLAELRD LVINQQKRVL VDFSQISDAE GQAEMQAQFR KAYGVGFANQ FIVITEHKGE 
121:	LLFTPFDQAE EVDPQLLEAP RTARLLARSG FASPAPANSE TNTLPHVAFY ISVNRAISDE 
181:	ECTFNNSWLW KNEKGSRPFC KDANISLIYR VNLERSLQYG IVGSATPDAK IVRISLDDDS 
241:	TGAGIHLNDQ LGYRQFGASY TTLDAYFREW STDAIAQDYR FVFNASNNKA QILKTFPVDN 
301:	INEKFERKEV SGFELGVTGG VEVSGDGPKA KLEARASYTQ SRWLTYNTQD YRIERNAKNA 
361:	QAVSFTWNRQ QYATAESLLN RSTDALWVNT YPVDVNRISP LSYASFVPKM DVIYKASATE 
421:	TGSTDFIIDS SVNIRPIYNG AYKHYYVVGA HQSYHGFEDT PRRRITKSAS FTVDWDHPVF 
481:	TGGRPVNLQL ASFNNRCIQV DAQGRLAANT CDSQQSAQSF IYDQLGRYVS ASNTKLCLDG 
541:	EALDALQPCN QNLTQRWEWR KGTDELTNVY SGESLGHDKQ TGELGLYASS NDAVSLRTIT 
601:	AYTDVFNAQE SSPILGYTQG KMNQQRVGQD HRLYVRAGAA IDALGSASDL LVGGNGGSLS 
661:	SVDLSGVKSI TATSGDFQYG GQQLVALTFT YQDGRQQTVG SKAYVTNAHE DRFDLPAAAK 
721:	ITQLKIWSDD WLVKGVQFDL N