Leucine-rich repeats of bacterial surface proteins serve as common pattern recognition motifs of human scavenger receptor gp340.
Scavenger receptors are innate immune molecules recognizing and inducing the clearance of non-host as well as modified host molecules. To recognize a wide pattern of invading microbes, many scavenger receptors bind to common pathogen-associated molecular patterns, such as lipopolysaccharides and lipoteichoic acids. Similarly, the gp340/DMBT1 protein, a member of the human scavenger receptor cysteine-rich protein family, displays a wide ligand repertoire. The peptide motif VEVLXXXXW derived from its scavenger receptor cysteine-rich domains is involved in some of these interactions, but most of the recognition mechanisms are unknown. In this study, we used mass spectrometry sequencing, gene inactivation, and recombinant proteins to identify Streptococcus pyogenes protein Spy0843 as a recognition receptor of gp340. Antibodies against Spy0843 are shown to protect against S. pyogenes infection, but no function or host receptor have been identified for the protein. Spy0843 belongs to the leucine-rich repeat (Lrr) family of eukaryotic and prokaryotic proteins. Experiments with truncated forms of the recombinant proteins confirmed that the Lrr region is needed in the binding of Spy0843 to gp340. The same motif of two other Lrr proteins, LrrG from the Gram-positive S. agalactiae and BspA from the Gram-negative Tannerella forsythia, also mediated binding to gp340. Moreover, inhibition of Spy0843 binding occurred with peptides containing the VEVLXXXXW motif, but also peptides devoid of the XXXXW motif inhibited binding of Lrr proteins. These results thus suggest that the conserved Lrr motif in bacterial proteins serves as a novel pattern recognition motif for unique core peptides of human scavenger receptor gp340.
Loimaranta
Vuokko
V
Departments of Medical Biochemistry and Genetics, Institute of Dentistry, University of Turku, Kiinamyllynkatu 10, FI-20520 Turku, Finland. vuokko.loimaranta@utu.fi
Hytönen
Jukka
J
Pulliainen
Arto T
AT
Sharma
Ashu
A
Tenovuo
Jorma
J
Strömberg
Nicklas
N
Finne
Jukka
J
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry; D002135:Calcium-Binding Proteins; D003545:Cysteine / Q000737:chemistry; D004268:DNA-Binding Proteins; D006801:Humans; D007930:Leucine / Q000737:chemistry*; D008024:Ligands; D008070:Lipopolysaccharides / Q000737:chemistry; D013058:Mass Spectrometry / Q000379:methods; D008969:Molecular Sequence Data; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000737:chemistry* / Q000502:physiology; D017386:Sequence Homology, Amino Acid; D013292:Streptococcus agalactiae / Q000378:metabolism; D013297:Streptococcus pyogenes / Q000378:metabolism; D025521:Tumor Suppressor Proteins
D001426:Bacterial Proteins; D002135:Calcium-Binding Proteins; C108174:DMBT1 protein, human; D004268:DNA-Binding Proteins; D008024:Ligands; D008070:Lipopolysaccharides; D011956:Receptors, Cell Surface; D025521:Tumor Suppressor Proteins; D007930:Leucine; D003545:Cysteine