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1.C.3.1.1
α-Hemolysin (alpha haemolysin; Hly; Hla; α-toxin). Fragments (13-293 aas) form heptamers like the native full length protein, but a fragment with aas 72-293 formed heptamers, octamers and nonamers. All formed Cl- permeable β-barrel channels (Vécsey-Semjén et al., 2010). The 3-d structure is available (PDB#7AHL). Both symmetry and size of cyclodextrin inhibitors and the toxin pore are important for effective inhibition (Yannakopoulou et al., 2011).  Oxoxylin A inhibits hemolysis by hindering self assembly of the hepatmeric pore in which two β-strands are contributed by each subunit (Song et al. 1996; Dong et al. 2013).  Applications of pore-forming α-haemolysin include small- and macromolecule-sensing, targeted cancer therapy, and drug delivery (Gurnev and Nestorovich 2014). Sugawara et al. 2015 studied pore formation. Structural comparisons among monomer, prepore and pore revealed a series of motions in which the N-terminal amino latch released upon oligomerization destroys its own key hydrogen bond betweem Asp45 and Try118. This action initiates the protrusion of the prestem. A Y118F mutant and the N-terminal truncated mutant markedly decreased the hemolytic activity, indicating the importance of the key hydrogen bond and the N-terminal amino latch for pore formation. A dynamic molecular mechanism of pore formation was proposed (Sugawara et al. 2015). Release of ATP from cells may occur directly through transmembrane pores formed by α-toxin (Baaske et al. 2016).

Accession Number:P09616
Protein Name:HLY aka HLA
Length:319
Molecular Weight:35904.00
Species:Staphylococcus aureus [1280]
Number of TMSs:1
Location1 / Topology2 / Orientation3: Secreted1
Substrate Cl-, small molecules, ATP

Cross database links:

Pfam: PF07968   

Gene Ontology

GO:0005576 C:extracellular region
GO:0019835 P:cytolysis
GO:0019836 P:hemolysis by symbiont of host erythrocytes
GO:0009405 P:pathogenesis

References (7)

[1] “Primary sequence of the alpha-toxin gene from Staphylococcus aureus wood 46.”  Gray G.S.et.al.   6500704
[2] “Functional expression of the alpha-hemolysin of Staphylococcus aureus in intact Escherichia coli and in cell lysates. Deletion of five C-terminal amino acids selectively impairs hemolytic activity.”  Walker B.et.al.   1587866
[3] “Structure of staphylococcal alpha-hemolysin, a heptameric transmembrane pore.”  Song L.et.al.   8943190
[4] “Assembly of the oligomeric membrane pore formed by Staphylococcal alpha-hemolysin examined by truncation mutagenesis.”  Walker B.et.al.   1400487
[5] “Site-directed mutagenesis of the alpha-toxin gene of Staphylococcus aureus: role of histidines in toxin activity in vitro and in a murine model.”  Menzies B.E.et.al.   8168947
[6] “Histidine residues near the N-terminus of staphylococcal alpha-toxin as reporters of regions that are critical for oligomerization and pore formation.”  Jursch R.et.al.   8188346
[7] “Key residues for membrane binding, oligomerization, and pore forming activity of staphylococcal alpha-hemolysin identified by cysteine scanning mutagenesis and targeted chemical modification.”  Walker B.et.al.   7559447
Structure:
7AHL   3M2L   3M3R   3M4D   3M4E   4IDJ   4YHD   3anz     

External Searches:

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  • Search COGs (Clusters of Orthologous Groups of proteins)
  • 2° Structure (Network Protein Sequence Analysis)

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Predict TMSs (Predict number of transmembrane segments)
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FASTA formatted sequence
1:	MKTRIVSSVT TTLLLGSILM NPVAGAADSD INIKTGTTDI GSNTTVKTGD LVTYDKENGM 
61:	HKKVFYSFID DKNHNKKLLV IRTKGTIAGQ YRVYSEEGAN KSGLAWPSAF KVQLQLPDNE 
121:	VAQISDYYPR NSIDTKEYMS TLTYGFNGNV TGDDTGKIGG LIGANVSIGH TLKYVQPDFK 
181:	TILESPTDKK VGWKVIFNNM VNQNWGPYDR DSWNPVYGNQ LFMKTRNGSM KAADNFLDPN 
241:	KASSLLSSGF SPDFATVITM DRKASKQQTN IDVIYERVRD DYQLHWTSTN WKGTNTKDKW 
301:	TDRSSERYKI DWEKEEMTN