Abstract
Streptococcus pneumoniae is a major human pathogen, and a leading cause of disease and death worldwide. Pneumococcal invasive disease is triggered by initial asymptomatic colonization of the human upper respiratory tract. The pneumococcal serine-rich repeat protein (PsrP) is a lung-specific virulence factor whose functional binding region (BR) binds to keratin-10 (KRT10) and promotes pneumococcal biofilm formation through self-oligomerization. We present the crystal structure of the KRT10-binding domain of PsrP (BR187–385) determined to 2.0 Å resolution. BR187–385 adopts a novel variant of the DEv-IgG fold, typical for microbial surface components recognizing adhesive matrix molecules adhesins, despite very low sequence identity. An extended β-sheet on one side of the compressed, two-sided barrel presents a basic groove that possibly binds to the acidic helical rod domain of KRT10. Our study also demonstrates the importance of the other side of the barrel, formed by extensive well-ordered loops and stabilized by short β-strands, for interaction with KRT10.
Highlights
Streptococcus pneumoniae is a human-adapted, Gram-positive commensal bacterium that colonizes the upper respiratory tract in about 10%& 2014 The Authors
Single anomalous dispersion (SAD) data, collected from a seleno-methionine derivative of the P43212 crystal form that diffracted to 2.25 A, was used to solve the phase problem
Three BR187– 385 polypeptide chains were placed in the asymmetric unit, and refined to R- and Rfree-values of 18.6% and 21.5%, respectively
Summary
Streptococcus pneumoniae is a major human pathogen, and a leading cause of disease and death worldwide. Pneumococcal invasive disease is triggered by initial asymptomatic colonization of the human upper respiratory tract. The pneumococcal serine-rich repeat protein (PsrP) is a lung-specific virulence factor whose functional binding region (BR) binds to keratin-10 (KRT10) and promotes pneumococcal biofilm formation through self-oligomerization. We present the crystal structure of the KRT10-binding domain of PsrP (BR187 – 385) determined to 2.0 Aresolution. An extended b-sheet on one side of the compressed, two-sided barrel presents a basic groove that possibly binds to the acidic helical rod domain of KRT10. Our study demonstrates the importance of the other side of the barrel, formed by extensive well-ordered loops and stabilized by short b-strands, for interaction with KRT10
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