6XJA

Streptococcus Pneumoniae IgA1 Protease with IgA1 substrate

Summary for 6XJA

• Entry DOI: 10.2210/pdb6xja/pdb
• EMDB information: 22204
• Descriptor: Immunoglobulin A1 protease, Immunoglobulin heavy constant alpha 1, Immunoglobulin alpha-1 light chain, ... (4 entities in total)
• Functional Keywords: iga1, complex, protease, metalloprotease, immune system
• Biological source: Streptococcus pneumoniae (strain ATCC BAA-255 / R6); More
• Total number of polymer chains: 5
• Total formula weight: 235580.34

Authors

Eisenmesser, E.Z.,Zheng, H. (deposition date: 2020-06-23, release date: 2021-01-20)

Primary citation

Wang, Z.,Rahkola, J.,Redzic, J.S.,Chi, Y.C.,Tran, N.,Holyoak, T.,Zheng, H.,Janoff, E.,Eisenmesser, E.
Mechanism and inhibition of Streptococcus pneumoniae IgA1 protease.
Nat Commun, 11:6063-6063, 2020

PubMed Abstract: 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.

PubMed: 33247098
DOI: 10.1038/s41467-020-19887-3

Experimental method

ELECTRON MICROSCOPY (4 Å)