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

Abstract

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-concentrationmore » 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.« less

Authors:

Lam, Kwok-ho  ^[1];

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• Search DOE PAGES for ORCID "0000-0002-7173-6600"

Qi, Ruifeng ^[1]; Liu, Shun ^[1]; Kroh, Amelie ^[2]; Yao, Guorui  ^[1];

• Search DOE PAGES for author "Yao, Guorui"
• Search DOE PAGES for ORCID "0000-0003-1839-9446"

Perry, Kay ^[3]; Rummel, Andreas  ^[2];

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• Search DOE PAGES for ORCID "0000-0002-0645-1641"

Jin, Rongsheng  ^[1]

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• Search DOE PAGES for ORCID "0000-0003-0348-7363"

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+ Show Author Affiliations

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)

Publication Date:

Mon Oct 16 00:00:00 EDT 2017

Research Org.:

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 Org.:

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)

OSTI Identifier:

1434740

Alternate Identifier(s):

OSTI ID: 1549483

Grant/Contract Number:  

R01AI091823; R01AI125704; R21AI123920; P41 GM103403; S10OD021527; AC02-06CH11357; AC02-76SF00515; P41GM103393

Resource Type:

Accepted Manuscript

Journal Name:

Toxicon

Additional Journal Information:

Journal Volume: 147; Journal Issue: C; Journal ID: ISSN 0041-0101

Country of Publication:

United States

Language:

ENGLISH

Subject:

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