α-hemolysin

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Alpha hemolysin
Alpha hemolysin
according to PDB  7AHL
other names

Alpha toxin ( S. aureus ), Hla

Existing structure data : PDB  3M2L , PDB  3M3R , PDB  3M4D

Mass / length primary structure 319 amino acids , 35,904 Da
Secondary to quaternary structure heptamer
Identifier
External IDs
Orthologue ( Staphylococcus aureus )
Entrez SAOUHSC_01121
UniProt P09616


PubMed search SAOUHSC_01121

α-Hemolysin (synonym α-toxin from S. aureus ) is a microbial exotoxin from Staphylococcus aureus .

properties

α-Hemolysin is a heptameric pore-forming toxin from the group of β-pore-forming toxins. It acts as a hemolysin . It is a virulence factor in infection with S. aureus . The virulence is proportional to the formation of α-hemolysin. In addition to the Panton Valentine leukocidine , it is a main virulence factor in pneumonia caused by infection with S. aureus . It is also involved in necrosis of the skin and in fatal courses in infections with S. aureus .

Structurally, α-hemolysin consists of 68% β-sheets and 10% α-helices . Each of the seven subunits is involved with two β-sheets in the formation of the pore in the form of a β-barrel , with hydrophilic amino acids on the inside of the pore. The diameter of the pore varies from 14 angstroms at the narrowest point to 46 Å at its widest point. The pore prefers anions .

The toxin effect arises through activation of the intrinsic pathway of apoptosis . In addition, α-hemolysin binds to ADAM10 .

application

Alpha-hemolysin was an early subject of investigation in the development of nanopore sequencing .

literature

Individual evidence

  1. ^ S. Bhakdi, J. Tranum-Jensen: Alpha-toxin of Staphylococcus aureus. In: Microbiological reviews. Volume 55, Number 4, December 1991, pp. 733-751, PMID 1779933 , PMC 372845 (free full text).
  2. ^ A b J. Bubeck Wardenburg, O. Schneewind: Vaccine protection against Staphylococcus aureus pneumonia. In: The Journal of experimental medicine. Volume 205, number 2, February 2008, pp. 287-294, doi : 10.1084 / jem.20072208 , PMID 18268041 , PMC 2271014 (free full text).
  3. ↑ J. Bubeck Wardenburg, T. Bae, M. Otto, FR Deleo, O. Schneewind: Poring over pores: alpha-hemolysin and Panton-Valentine leukocidin in Staphylococcus aureus pneumonia. In: Nature medicine. Volume 13, Number 12, December 2007, pp. 1405-1406, doi : 10.1038 / nm1207-1405 , PMID 18064027 .
  4. ↑ a b B. J. Berube, J. Bubeck Wardenburg: Staphylococcus aureus α-toxin: nearly a century of intrigue. In: Toxins. Volume 5, Number 6, June 2013, pp. 1140-1166, PMID 23888516 , PMC 3717774 (free full text).
  5. ^ A b L. Song, MR Hobaugh, C. Shustak, S. Cheley, H. Bayley, JE Gouaux: Structure of staphylococcal alpha-hemolysin, a heptameric transmembrane pore. In: Science. Volume 274, Number 5294, December 1996, pp. 1859-1866, PMID 8943190 .
  6. ↑ G. Menestrina, M. Dalla Serra, M. Comai, M. Coraiola, G. Viero, S. Werner, DA Colin, H. Monteil, G. Prévost: Ion channels and bacterial infection: the case of beta-barrel pore -forming protein toxins of Staphylococcus aureus. In: FEBS letters. Volume 552, Number 1, September 2003, pp. 54-60, PMID 12972152 .
  7. ↑ H. Bantel, B. Sinha, W. Domschke, G. Peters, K. Schulze-Osthoff, RU Jänicke: alpha-Toxin is a mediator of Staphylococcus aureus-induced cell death and activates caspases via the intrinsic death pathway independently of death receptor signaling. In: Journal of Cell Biology . Volume 155, number 4, November 2001, pp. 637-648, doi : 10.1083 / jcb.200105081 , PMID 11696559 , PMC 2198876 (free full text).
  8. ↑ JJ Kasianowicz, E. Brandin, D. Branton, DW Deamer: Characterization of individual polynucleotide molecules using a membrane channel. In: Proceedings of the National Academy of Sciences . Volume 93, Number 24, November 1996, pp. 13770-13773, PMID 8943010 , PMC 19421 (free full text).
  9. ↑ J. Nivala, DB Marks, M. Akeson: Unfoldase-mediated protein translocation through an α-hemolysin nanopore. In: Nature Biotechnology . Volume 31, number 3, March 2013, pp. 247-250, doi : 10.1038 / nbt.2503 , PMID 23376966 , PMC 3772521 (free full text).