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-Structure paper
タイトル | High-resolution structure of native toxin A from Clostridioides difficile. |
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ジャーナル・号・ページ | EMBO Rep, Vol. 23, Issue 1, Page e53597, Year 2022 |
掲載日 | 2022年1月5日 |
![]() | Aria Aminzadeh / Christian Engelbrecht Larsen / Thomas Boesen / René Jørgensen / ![]() |
PubMed 要旨 | Clostridioides difficile infections have emerged as the leading cause of healthcare-associated infectious diarrhea. Disease symptoms are mainly caused by the virulence factors, TcdA and TcdB, which ...Clostridioides difficile infections have emerged as the leading cause of healthcare-associated infectious diarrhea. Disease symptoms are mainly caused by the virulence factors, TcdA and TcdB, which are large homologous multidomain proteins. Here, we report a 2.8 Å resolution cryo-EM structure of native TcdA, unveiling its conformation at neutral pH. The structure uncovers the dynamic movement of the CROPs domain which is induced in response to environmental acidification. Furthermore, the structure reveals detailed information about the interaction area between the CROPs domain and the tip of the delivery and receptor-binding domain, which likely serves to shield the C-terminal part of the hydrophobic pore-forming region from solvent exposure. Similarly, extensive interactions between the globular subdomain and the N-terminal part of the pore-forming region suggest that the globular subdomain shields the upper part of the pore-forming region from exposure to the surrounding solvent. Hence, the TcdA structure provides insights into the mechanism of preventing premature unfolding of the pore-forming region at neutral pH, as well as the pH-induced inter-domain dynamics. |
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手法 | EM (単粒子) |
解像度 | 2.83 Å |
構造データ | EMDB-13574, PDB-7pog: |
化合物 | ![]() ChemComp-ZN: |
由来 |
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![]() | TOXIN / glucosyltransferase |