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-Structure paper
タイトル | Structure of the Anthrax Protective Antigen D425A Dominant Negative Mutant Reveals a Stalled Intermediate State of Pore Maturation. |
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ジャーナル・号・ページ | J Mol Biol, Vol. 434, Issue 9, Page 167548, Year 2022 |
掲載日 | 2022年5月15日 |
著者 | Harry Scott / Wei Huang / Kiran Andra / Sireesha Mamillapalli / Srinivas Gonti / Alexander Day / Kaiming Zhang / Nurjahan Mehzabeen / Kevin P Battaile / Anjali Raju / Scott Lovell / James G Bann / Derek J Taylor / |
PubMed 要旨 | The tripartite protein complex produced by anthrax bacteria (Bacillus anthracis) is a member of the AB family of β-barrel pore-forming toxins. The protective antigen (PA) component forms an ...The tripartite protein complex produced by anthrax bacteria (Bacillus anthracis) is a member of the AB family of β-barrel pore-forming toxins. The protective antigen (PA) component forms an oligomeric prepore that assembles on the host cell surface and serves as a scaffold for binding of lethal and edema factors. Following endocytosis, the acidic environment of the late endosome triggers a pH-induced conformational rearrangement to promote maturation of the PA prepore to a functional, membrane spanning pore that facilitates delivery of lethal and edema factors to the cytosol of the infected host. Here, we show that the dominant-negative D425A mutant of PA stalls anthrax pore maturation in an intermediate state at acidic pH. Our 2.7 Å cryo-EM structure of the intermediate state reveals structural rearrangements that involve constriction of the oligomeric pore combined with an intramolecular dissociation of the pore-forming module. In addition to defining the early stages of anthrax pore maturation, the structure identifies asymmetric conformational changes in the oligomeric pore that are influenced by the precise configuration of adjacent protomers. |
リンク | J Mol Biol / PubMed:35304125 |
手法 | EM (単粒子) / X線回折 |
解像度 | 2.9 - 5.5 Å |
構造データ | EMDB-25489: cryoEM map of PA D425A mutant at pH 5.5 D7 symmetry class 1 EMDB-25490: dimer of heptamer class 2 EMDB-25491: heptamer of D425A mutant at pH 5.5 PDB-6uji: |
由来 |
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キーワード | TOXIN / Anthrax Toxin / PA63 heptamer |