title: The basic keratin 10-binding domain of the virulence-associated pneumococcal serine-rich protein PsrP adopts a novel MSCRAMM fold.
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.
authors.affiliation: Science for Life Laboratory, Center for Infectious Medicine (CIM), Department of Medicine, Karolinska University Hospital Huddinge, Karolinska Institutet Science Park, Tomtebodavägen 23A Solna, Stockholm 17165, Sweden.
authors.forename: Tim
authors.initials: T
authors.lastname: Schulte
authors.forename: Jonas
authors.initials: J
authors.lastname: Löfling
authors.forename: Cecilia
authors.initials: C
authors.lastname: Mikaelsson
authors.forename: Alexey
authors.initials: A
authors.lastname: Kikhney
authors.forename: Karina
authors.initials: K
authors.lastname: Hentrich
authors.forename: Aurora
authors.initials: A
authors.lastname: Diamante
authors.forename: Christine
authors.initials: C
authors.lastname: Ebel
authors.forename: Staffan
authors.initials: S
authors.lastname: Normark
authors.forename: Dmitri
authors.initials: D
authors.lastname: Svergun
authors.forename: Birgitta
authors.initials: B
authors.lastname: Henriques-Normark
authors.forename: Adnane
authors.initials: A
authors.lastname: Achour
mesh_terms: D018829:Adhesins, Bacterial / Q000737:chemistry / Q000378:metabolism; D000409:Alanine / Q000235:genetics / Q000378:metabolism; D019943:Amino Acid Substitution; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018360:Crystallography, X-Ray; D006801:Humans; D053550:Keratin-10 / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D011485:Protein Binding; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D055672:Static Electricity; D013296:Streptococcus pneumoniae / Q000378:metabolism; D037521:Virulence Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D018829:Adhesins, Bacterial; D001426:Bacterial Proteins; D037521:Virulence Factors; D053550:Keratin-10; D000409:Alanine
keywords: MSCRAMM; PsrP; Streptococcus pneumoniae; adhesion; bacterial virulence factor; keratin-10