The hypothetical protein P47 of Clostridium botulinum E1 strain Beluga has a structural topology similar to bactericidal/permeability-increasing protein

Journal Article · Mon Oct 16 00:00:00 EDT 2017 · Toxicon

DOI:https://doi.org/10.1016/j.toxicon.2017.10.012· OSTI ID:1434740

Lam, Kwok-ho  ^[1]; Qi, Ruifeng ^[1]; Liu, Shun ^[1]; Kroh, Amelie ^[2]; Yao, Guorui  ^[1]; Perry, Kay ^[3]; Rummel, Andreas  ^[2]; Jin, Rongsheng  ^[1]

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1. Univ. of California, Irvine, CA (United States)
2. Medizinische Hochschule Hannover (Germany). Inst. für Toxikologie
3. Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS), Northeastern Collaborative Access Team (NE-CAT) and Department of Chemistry and Chemical Biology; Cornell Univ., Ithaca, NY (United States)

Botulinum neurotoxins (BoNTs) are causative agents of the life-threatening disease botulism. They are naturally produced by species of the bacteria Clostridium botulinum as stable and non-covalent complexes, in which the BoNT molecule is assembled with several auxiliary non-toxic proteins. Some BoNT serotypes, represented by the well-studied BoNT serotype A (BoNT/A), are produced by Clostridium strains that carry the ha gene cluster, which encodes four neurotoxin-associated proteins (NTNHA, HA17, HA33, and HA70) that play an important role to deliver and protect BoNTs in the gastrointestinal tract during oral intoxication. In contrast, BoNT/E- and BoNT/F-producing strains carry a distinct gene cluster that encodes five proteins (NTNHA, P47, OrfX1, OrfX2, and OrfX3, termed the $orfX$ cluster). The structures and functions of these proteins remain largely unknown. In this paper, we report the crystal structure of P47 resolved at 2.8 Å resolution. Surprisingly, P47 displays a structural topology that is similar to bactericidal/permeability-increasing (BPI) like proteins, which were previously identified only in eukaryotes. The similarity of a hydrophobic cleft of P47 with the phospholipid-binding groove of BPI suggests that P47 might be involved in lipid association to exert its function. Consistently, P47 associates and induces aggregation of asolectin-containing liposomes in a protein- and lipid-concentration dependent manner. These findings laid the foundation for future structural and functional studies of the potential roles of P47 and OrfX proteins in facilitating oral intoxication of BoNTs.

• Research Organization: Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS); SLAC National Accelerator Laboratory (SLAC), Menlo Park, CA (United States). Stanford Synchrotron Radiation Lightsource (SSRL)
• Sponsoring Organization: USDOE Office of Science (SC), Basic Energy Sciences (BES); USDOE Office of Science (SC), Biological and Environmental Research (BER); Swiss Federal Office for Civil Protection (FOCP); National Institute of General Medical Sciences (NIGMS); National Institute of Allergy and Infectious Diseases (NIAID); National Institutes of Health (NIH)
• Grant/Contract Number: R01AI091823; R01AI125704; R21AI123920; P41 GM103403; S10OD021527; AC02-06CH11357; AC02-76SF00515; P41GM103393
• OSTI ID: 1434740
• Alternate ID(s): OSTI ID: 1549483
• Journal Information: Toxicon, Vol. 147, Issue C; ISSN 0041-0101
• Country of Publication: United States
• Language: ENGLISH

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
Botulinum neurotoxin
Crystal structure
Bactericidal/permeability-increasing protein
Toxin complex
orfX gene cluster
P47
Lipid binding