The Crystal Structure of the Bacillus anthracis Spore Surface Protein BclA Shows Remarkable Similarity to Mammalian Proteins

Laboratoire de Biotechnologies et Pharmacologie Génétique Appliquées, CNRS, Unité Mixte de Recherche 8113, Ecole Normale Supérieure de Cachan, 61 Avenue du Président Wilson, 94235 Cachan, France.
Journal of Biological Chemistry (Impact Factor: 4.57). 01/2006; 280(52):43073-8. DOI: 10.1074/jbc.M510087200
Source: PubMed


The lethal disease anthrax is propagated by spores of Bacillus anthracis, which can penetrate into the mammalian host by inhalation, causing a rapid progression of the disease and a mostly fatal
outcome. We have solved the three-dimensional structure of the major surface protein BclA on B. anthracis spores. Surprisingly, the structure resembles C1q, the first component of complement, despite there being no sequence homology.
Although most assays for C1q-like activity, including binding to C1q receptors, suggest that BclA does not mimic C1q, we show
that BclA, as well as C1q, interacts with components of the lung alveolar surfactant layer. Thus, to better recognize and
invade its hosts, this pathogenic soil bacterium may have evolved a surface protein whose structure is strikingly close to
a mammalian protein.

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Available from: David J S Hulmes, Jun 29, 2014
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    • "A trimer of BxpB (17.3 kDa  3 = 51.9 kDa) would correspond to a volume of 64 nm 3 , or a sphere of approximately 5 nm diameter – similar in size to the protrusions in the basal layer and about the same as the size of the BclA trimer comprising the filament knob (Rety et al., 2005). BxpB is clearly not a primary structural component of the basal layer because DbxpB spores possess an intact and stable basal layer with the same bilayered appearance of wildtype and DbclA basal layers. "
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    ABSTRACT: Bacillus anthracis and other pathogenic Bacillus species form spores that are surrounded by an exosporium, a balloon-like layer that acts as the outer permeability barrier of the spore and contributes to spore survival and virulence. The exosporium consists of a hair-like nap and a paracrystalline basal layer. The filaments of the nap are comprised of trimers of the collagen-like glycoprotein BclA, while the basal layer contains approximately 20 different proteins. One of these proteins, BxpB, forms tight complexes with BclA and is required for attachment of essentially all BclA filaments to the basal layer. Another basal layer protein, ExsB, is required for the stable attachment of the exosporium to the spore. To determine the organization of BclA and BxpB within the exosporium, we used cryo-electron microscopy, cryo-sectioning and crystallographic analysis of negatively stained exosporium fragments to compare wildtype spores and mutant spores lacking BclA, BxpB or ExsB (ΔbclA, ΔbxpB and ΔexsB spores, respectively). The trimeric BclA filaments are attached to basal layer surface protrusions that appear to be trimers of BxpB. The protrusions interact with a crystalline layer of hexagonal subunits formed by other basal layer proteins. Although ΔbxpB spores retain the hexagonal subunits, the basal layer is not organized with crystalline order and lacks basal layer protrusions and most BclA filaments, indicating a central role for BxpB in exosporium organization.
    Full-text · Article · Mar 2014 · Journal of Structural Biology
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    • "For example, the three-dimensional structure of the major surface protein of Bacillus anthracis spore surface protein, bacillus collagen-like protein of anthracis (BclA) reveals remarkable similarity to C1q – although there is only low sequence identity between the two proteins (Sylvestre et al., 2002; Rety et al., 2005). Furthermore, both BclA and C1q have been shown to bind to lung alveolar surfactant component-SP-C, suggesting that both recognize common targets in the alveolar component (Rety et al., 2005). This molecular mimicry in turn, underscores not only the functional relevance of the gC1q domain, but also pathogenic microorganisms mimic this signature domain in order to get access into host cells. "
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    ABSTRACT: Research conducted over the past 20 years have helped us unravel not only the hidden structural and functional subtleties of human C1q, but also has catapulted the molecule from a mere recognition unit of the classical pathway to a well-recognized molecular sensor of damage-modified self or non-self antigens. Thus, C1q is involved in a rapidly expanding list of pathological disorders - including autoimmunity, trophoblast migration, preeclampsia, and cancer. The results of two recent reports are provided to underscore the critical role C1q plays in health and disease. First is the observation by Singh et al. (2011) showing that pregnant C1q-/- mice recapitulate the key features of human preeclampsia that correlate with increased fetal death. Treatment of the C1q-/- mice with pravastatin restored trophoblast invasiveness, placental blood flow, and angiogenic balance and, thus, prevented the onset of preeclampsia. Second is the report by Hong et al. (2009) which showed that C1q can induce apoptosis of prostate cancer cells by activating the tumor suppressor molecule WW-domain containing oxydoreductase (WWOX or WOX1) and destabilizing cell adhesion. Downregulation of C1q on the other hand, enhanced prostate hyperplasia and cancer formation due to failure of WOX1 activation. C1q belongs to a family of structurally and functionally related TNF-α-like family of proteins that may have arisen from a common ancestral gene. Therefore C1q not only shares the diverse functions with the tumor necrosis factor family of proteins, but also explains why C1q has retained some of its ancestral "cytokine-like" activities. This review is intended to highlight some of the structural and functional aspects of C1q by underscoring the growing list of its non-traditional functions.
    Full-text · Article · Apr 2012 · Frontiers in Immunology
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    • "Analyses of B. anthracis and B. cereus spores have identified 20 exosporium-associated proteins and glycoproteins (Boydston et al., 2005; Redmond et al., 2004; Steichen et al., 2003, 2005; Sylvestre et al., 2002, 2005; Todd et al., 2003). The major immunodominant component of the hair-like fibers is the BclA (Bacillus collagenlike protein of anthrax) glycoprotein, the conformation of which mimics that of the C1q component of complement (Daubenspeck et al., 2004; Rety et al., 2005; Steichen et al., 2003). BclA (21 kD) has a collagen-like region (CLR), a proline-rich sequence, and is a member of the tumor necrosis factor family, which is characterized by a trimeric, jelly-roll fold. "

    Full-text · Chapter · Nov 2010
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