IngentaConnect Crystallographic studies of the anthrax lethal toxin

Authors: Liddington, R.¹; Pannifer, A.¹; Hanna, P.²; Leppla, S.³; Collier, R. J.⁴

Source: Journal of Applied Microbiology, Volume 87, Number 2, August 1999 , pp. 282-282(1)

Abstract:

Anthrax lethal toxin comprises two proteins: protective antigen (PA; MW 83 kDa) and lethal factor (LF; MW 87 kDa). We have recently determined the crystal structure of the 735-residue PA in its monomeric and heptameric forms ( Petosa et al. 1997 ). It bears no resemblance to other bacterial toxins of known three-dimensional structure, and defines a new structural class which includes homologous toxins from other Gram-positive bacteria. We have proposed a model of membrane insertion in which the water-soluble heptamer undergoes a substantial pH-induced conformational change involving the creation of a 14-stranded β-barrel. Recent work by Collier's group ( Benson et al. 1998 ) lends strong support to our model of membrane insertion. `Lethal factor' is the catalytic component of anthrax lethal toxin. It binds to the surface of the cell-bound PA heptamer and, following endocytosis and acidification of the endosome, translocates to the cytosol. We have made substantial progress towards an atomic resolution crystal structure of LF. Progress towards a structure of the 7:7 translocation complex between the PA heptamer and LF will also be discussed.

Document Type: Research article

DOI: 10.1046/j.1365-2672.1999.00888.x

Affiliations: 1: Department of Biochemistry, University of Leicester, Leicester, UK, 2: Duke University Medical Center, Durham, NC, 3: Laboratory of Microbial Ecology, National Institutes of Health, Bethesda, MD and 4: Department of Microbiology & Molecular Genetics, Harvard Medical School, Boston, MA, USA

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