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-Structure paper
タイトル | Mechanism and inhibition of Streptococcus pneumoniae IgA1 protease. |
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ジャーナル・号・ページ | Nat Commun, Vol. 11, Issue 1, Page 6063, Year 2020 |
掲載日 | 2020年11月27日 |
著者 | Zhiming Wang / Jeremy Rahkola / Jasmina S Redzic / Ying-Chih Chi / Norman Tran / Todd Holyoak / Hongjin Zheng / Edward Janoff / Elan Eisenmesser / |
PubMed 要旨 | Opportunistic pathogens such as Streptococcus pneumoniae secrete a giant metalloprotease virulence factor responsible for cleaving host IgA1, yet the molecular mechanism has remained unknown since ...Opportunistic pathogens such as Streptococcus pneumoniae secrete a giant metalloprotease virulence factor responsible for cleaving host IgA1, yet the molecular mechanism has remained unknown since their discovery nearly 30 years ago despite the potential for developing vaccines that target these enzymes to block infection. Here we show through a series of cryo-electron microscopy single particle reconstructions how the Streptococcus pneumoniae IgA1 protease facilitates IgA1 substrate recognition and how this can be inhibited. Specifically, the Streptococcus pneumoniae IgA1 protease subscribes to an active-site-gated mechanism where a domain undergoes a 10.0 Å movement to facilitate cleavage. Monoclonal antibody binding inhibits this conformational change, providing a direct means to block infection at the host interface. These structural studies explain decades of biological and biochemical studies and provides a general strategy to block Streptococcus pneumoniae IgA1 protease activity to potentially prevent infection. |
リンク | Nat Commun / PubMed:33247098 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.8 - 4.8 Å |
構造データ | EMDB-22204, PDB-6xja: EMDB-22205, PDB-6xjb: EMDB-22328, PDB-7jgj: |
由来 |
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キーワード | IMMUNE SYSTEM (免疫系) / IgA1 (免疫グロブリンA) / Complex / Protease (プロテアーゼ) / metalloprotease (金属プロテアーゼ) / neutralization |