AIP56 is a novel bacterial exotoxin acting by triggering apoptosis in both macrophages and neutrophils, resulting in lysis of these phagocytes by post-apoptotic secondary necrosis [1,2]. Recently, we showed that AIP56 is a zinc-metalloprotease AB-type toxin that targets NF-kB [3]. Exerting their enzymatic activity on intracellular targets, AB toxins enter cells through a multi-step process involving specific binding to the cell surface, internalization via receptor-mediated endocytosis, and translocation into the cytosol [4]. Thus, elucidating the structure of this toxin will potentially enable the use of AIP56, or engineered AIP56 derivatives, as pharmacological and biological tools [5,6].
The candidates should hold a PhD in Biochemistry, Molecular Biology, or a related field. Although not mandatory, preference will be given to candidates with experience in protein expression and purification, macromolecular crystallization or X-ray crystallography.
For additional information on FCT fellowships please visit http://www.fct.pt/apoios/bolsas/concursos/individuais2013.phtml.en. Any other enquiries should be addressed to Dr. N. Santos (nsantos_at_ibmc.up.pt).
1. do Vale A, Costa-Ramos C, Silva A, Silva
DS, Gartner F, et al. (2007) Systemic macrophage and neutrophil destruction
by secondary necrosis induced by a bacterial exotoxin in a Gram-negative
septicaemia. Cell Microbiol 9: 988-1003.
2. do Vale A, Silva MT, dos Santos NMS,
Nascimento DS, Reis-Rodrigues P, et al. (2005) AIP56, a novel plasmid-encoded
virulence factor of Photobacterium damselae subsp. piscicida with apoptogenic
activity against sea bass macrophages and neutrophils. Molecular Microbiology
58: 1025-1038.
3. Silva DS, Pereira LMG, Moreira AR, Ferreira-da-Silva
F, Brito RM, et al. (2013) The Apoptogenic
Toxin AIP56 Is a Metalloprotease A-B Toxin that Cleaves NF-ęb P65. PLoS
Pathog 9: e1003128.
4. Montecucco C, Papini E, Schiavo G (1994)
Bacterial protein toxins penetrate cells via a four-step mechanism. FEBS
Letters 346: 92-98.
5. Atassi MZ, Dolimbek BZ, Steward LE,
Aoki KR (2007) Molecular bases of protective immune responses against botulinum
neurotoxin A--how antitoxin antibodies block its action. Crit Rev Immunol
27: 319-341.
6. Holmgren J, Svennerholm A-M (2006) Engineered
bacterial toxin vaccines and adjuvants. In: Alouf JE, Popoff MR, editors.
The Comprehensive Sourcebook of Bacterial Protein Toxins: Academic Press.
pp. 1008-1018.
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Pedro J. B. Pereira, PhD
IBMC - Biomolecular Structure Group
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Portugal
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