The hypothetical protein P47 of Clostridium botulinum E1 strain Beluga has a structural topology similar to bactericidal/permeability-increasing protein
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...
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ftosti:oai:osti.gov:1434740 2023-07-30T04:02:39+02:00 The hypothetical protein P47 of Clostridium botulinum E1 strain Beluga has a structural topology similar to bactericidal/permeability-increasing protein Lam, Kwok-ho Qi, Ruifeng Liu, Shun Kroh, Amelie Yao, Guorui Perry, Kay Rummel, Andreas Jin, Rongsheng 2023-06-27 application/pdf http://www.osti.gov/servlets/purl/1434740 https://www.osti.gov/biblio/1434740 https://doi.org/10.1016/j.toxicon.2017.10.012 unknown http://www.osti.gov/servlets/purl/1434740 https://www.osti.gov/biblio/1434740 https://doi.org/10.1016/j.toxicon.2017.10.012 doi:10.1016/j.toxicon.2017.10.012 59 BASIC BIOLOGICAL SCIENCES 2023 ftosti https://doi.org/10.1016/j.toxicon.2017.10.012 2023-07-11T09:25:29Z 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. Other/Unknown Material Beluga Beluga* SciTec Connect (Office of Scientific and Technical Information - OSTI, U.S. Department of Energy) Toxicon 147 19 26 |
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SciTec Connect (Office of Scientific and Technical Information - OSTI, U.S. Department of Energy) |
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59 BASIC BIOLOGICAL SCIENCES |
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59 BASIC BIOLOGICAL SCIENCES Lam, Kwok-ho Qi, Ruifeng Liu, Shun Kroh, Amelie Yao, Guorui Perry, Kay Rummel, Andreas Jin, Rongsheng The hypothetical protein P47 of Clostridium botulinum E1 strain Beluga has a structural topology similar to bactericidal/permeability-increasing protein |
topic_facet |
59 BASIC BIOLOGICAL SCIENCES |
description |
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. |
author |
Lam, Kwok-ho Qi, Ruifeng Liu, Shun Kroh, Amelie Yao, Guorui Perry, Kay Rummel, Andreas Jin, Rongsheng |
author_facet |
Lam, Kwok-ho Qi, Ruifeng Liu, Shun Kroh, Amelie Yao, Guorui Perry, Kay Rummel, Andreas Jin, Rongsheng |
author_sort |
Lam, Kwok-ho |
title |
The hypothetical protein P47 of Clostridium botulinum E1 strain Beluga has a structural topology similar to bactericidal/permeability-increasing protein |
title_short |
The hypothetical protein P47 of Clostridium botulinum E1 strain Beluga has a structural topology similar to bactericidal/permeability-increasing protein |
title_full |
The hypothetical protein P47 of Clostridium botulinum E1 strain Beluga has a structural topology similar to bactericidal/permeability-increasing protein |
title_fullStr |
The hypothetical protein P47 of Clostridium botulinum E1 strain Beluga has a structural topology similar to bactericidal/permeability-increasing protein |
title_full_unstemmed |
The hypothetical protein P47 of Clostridium botulinum E1 strain Beluga has a structural topology similar to bactericidal/permeability-increasing protein |
title_sort |
hypothetical protein p47 of clostridium botulinum e1 strain beluga has a structural topology similar to bactericidal/permeability-increasing protein |
publishDate |
2023 |
url |
http://www.osti.gov/servlets/purl/1434740 https://www.osti.gov/biblio/1434740 https://doi.org/10.1016/j.toxicon.2017.10.012 |
genre |
Beluga Beluga* |
genre_facet |
Beluga Beluga* |
op_relation |
http://www.osti.gov/servlets/purl/1434740 https://www.osti.gov/biblio/1434740 https://doi.org/10.1016/j.toxicon.2017.10.012 doi:10.1016/j.toxicon.2017.10.012 |
op_doi |
https://doi.org/10.1016/j.toxicon.2017.10.012 |
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Toxicon |
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147 |
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19 |
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26 |
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1772813466148536320 |