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Deleted in Malignant Brain Tumors-1 Protein (DMBT1): A Pattern Recognition Receptor with Multiple Binding Sites
Periodontology and Oral Biochemistry, Academic Centre for Dentistry Amsterdam, G. Mahlerlaan 3004, 1081LA, Amsterdam, The Netherlands
Medical Biochemistry, University of Gothenburg, Gothenburg, Sweden Box 440, 40530 Gothenburg, Sweden
* Author to whom correspondence should be addressed.
Received: 11 November 2010; in revised form: 9 December 2010 / Accepted: 9 December 2010 / Published: 17 December 2010
Abstract: Deleted in Malignant Brain Tumors-1 protein (DMBT1), salivary agglutinin (DMBT1SAG), and lung glycoprotein-340 (DMBT1GP340) are three names for glycoproteins encoded by the same DMBT1 gene. All these proteins belong to the scavenger receptor cysteine-rich (SRCR) superfamily of proteins: a superfamily of secreted or membrane-bound proteins with SRCR domains that are highly conserved down to sponges, the most ancient metazoa. In addition to SRCR domains, all DMBT1s contain two CUB domains and one zona pellucida domain. The SRCR domains play a role in the function of DMBT1s, which is the binding of a broad range of pathogens including cariogenic streptococci, Helicobacter pylori and HIV. Mucosal defense proteins like IgA, surfactant proteins and lactoferrin also bind to DMBT1s through their SRCR domains. The binding motif on the SRCR domains comprises an 11-mer peptide in which a few amino acids are essential for binding (GRVEVLYRGSW). Adjacent to each individual SRCR domain are glycosylation domains, where the attached carbohydrate chains play a role in the binding of influenza A virus and Helicobacter pylori. The composition of the carbohydrate chains is not only donor specific, but also varies between different organs. These data demonstrate a role for DMBT1s as pattern recognition molecules containing various peptide and carbohydrate binding motifs.
Keywords: dental caries; innate immunity; mucosal protection; SRCR domains
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Ligtenberg, A.J.M.; Karlsson, N.G.; Veerman, E.C.I. Deleted in Malignant Brain Tumors-1 Protein (DMBT1): A Pattern Recognition Receptor with Multiple Binding Sites. Int. J. Mol. Sci. 2010, 11, 5212-5233.
Ligtenberg AJM, Karlsson NG, Veerman ECI. Deleted in Malignant Brain Tumors-1 Protein (DMBT1): A Pattern Recognition Receptor with Multiple Binding Sites. International Journal of Molecular Sciences. 2010; 11(12):5212-5233.
Ligtenberg, Antoon J. M.; Karlsson, Niclas G.; Veerman, Enno C. I. 2010. "Deleted in Malignant Brain Tumors-1 Protein (DMBT1): A Pattern Recognition Receptor with Multiple Binding Sites." Int. J. Mol. Sci. 11, no. 12: 5212-5233.