The basic keratin 10-binding domain of the virulence-associated pneumococcal serine-rich protein PsrP adopts a novel MSCRAMM fold.

Tim Schulte, Jonas Löfling, Cecilia Mikaelsson, Alexey Kikhney, Karina Hentrich, Aurora Diamante, Christine Ebel, Staffan Normark, Dmitri Svergun, Birgitta Henriques-Normark, Adnane Achour

Open biology 2014 Jan 15

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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.

Citation

Tim Schulte, Jonas Löfling, Cecilia Mikaelsson, Alexey Kikhney, Karina Hentrich, Aurora Diamante, Christine Ebel, Staffan Normark, Dmitri Svergun, Birgitta Henriques-Normark, Adnane Achour. The basic keratin 10-binding domain of the virulence-associated pneumococcal serine-rich protein PsrP adopts a novel MSCRAMM fold. Open biology. 2014 Jan 15;4:130090