Identification of the Bacteria-binding Peptide Domain on Salivary Agglutinin (gp-340/DMBT1), a Member of the Scavenger Receptor Cysteine-rich Superfamily

• Published in: The Journal of biological chemistry 2002-08, Vol.277 (35), p.32109-32115
• Main Authors: Bikker, Floris J, Ligtenberg, Antoon J M, Nazmi, Kamran, Veerman, Enno C I, van't Hof, Wim, Bolscher, Jan G M, Poustka, Annemarie, Nieuw Amerongen, Arie V, Mollenhauer, Jan
• Format: Article
• Language: English
• Subjects: Agglutination; Agglutinins; Amino Acid Sequence; Binding Sites; Calcium-Binding Proteins; Consensus Sequence; Cysteine; DNA-Binding Proteins; Humans; Lysine; Models, Molecular; Molecular Sequence Data; Parotid Gland - metabolism; Peptide Fragments - chemistry; Polymorphism, Genetic; Protein Conformation; Receptors, Cell Surface - chemistry; Receptors, Cell Surface - metabolism; Saliva - metabolism; Salivary Proteins and Peptides - chemistry; Salivary Proteins and Peptides - metabolism; Sequence Alignment; Sequence Homology, Amino Acid; Streptococcus mutans - physiology; Tumor Suppressor Proteins
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M203788200

Salivary agglutinin is encoded by DMBT1 and identical to gp-340, a member of the scavenger receptor cysteine-rich (SRCR) superfamily. Salivary agglutinin/DMBT1 is known for its Streptococcus mutans agglutinating properties. This 300–400 kDa glycoprotein is composed of conserved peptide motifs: 14 SRCR domains that are separated by SRCR-interspersed domains (SIDs), 2 CUB (C1r/C1s Uegf Bmp1) domains, and a zona pellucida domain. We have searched for the peptide domains of agglutinin/DMBT1 responsible for bacteria binding. Digestion with endoproteinase Lys-C resulted in a protein fragment containing exclusively SRCR and SID domains that binds to S. mutans. To define more closely the S. mutans- binding domain, consensus-based peptides of the SRCR domains and SIDs were designed and synthesized. Only one of the SRCR peptides, designated SRCRP2, and none of the SID peptides bound to S. mutans. Strikingly, this peptide was also able to induce agglutination of S. mutans and a number of other bacteria. The repeated presence of this peptide in the native molecule endows agglutinin/DMBT1 with a general bacterial binding feature with a multivalent character. Moreover, our studies demonstrate for the first time that the polymorphic SRCR domains of salivary agglutinin/DMBT1 mediate ligand interactions.