title: The scavenging capacity of DMBT1 is impaired by germline deletions.
abstract: The Scavenger Receptor Cysteine-Rich (SRCR) proteins are an archaic group of proteins characterized by the presence of multiple SRCR domains. They are membrane-bound or secreted proteins, which are generally related to host defense systems in animals. Deleted in Malignant Brain Tumors 1 (DMBT1) is a SRCR protein which is secreted in mucosal fluids and involved in host defense by pathogen binding by its SRCR domains. Genetic polymorphism within DMBT1 leads to DMBT1-alleles giving rise to polypeptides with interindividually different numbers of SRCR domains, ranging from 8 SRCR domains (encoded by 6 kb DMBT1 variant) to 13 SRCR domains (encoded by the 8 kb DMBT1 variant). In the present study, we have investigated whether reduction from 13 to 8 amino-terminal SRCR domains leads to reduction of bacterial binding. The 6 kb variant bound ~20-45% less bacteria compared to the 8 kb variant. These results support the hypothesis that genetic variation in DMBT1 may influence microbial defense.
authors.affiliation: Department of Oral Biochemistry, Academic Centre for Dentistry Amsterdam, University of Amsterdam and VU University Amsterdam, Gustav Mahlerlaan 3004, 1081LA, Amsterdam, Netherlands. fbikker@acta.nl.
authors.forename: Floris J
authors.initials: FJ
authors.lastname: Bikker
authors.affiliation: Division of Molecular Genome Analysis, German Cancer Research Center, Heidelberg, Germany.
authors.forename: Caroline
authors.initials: C
authors.lastname: End
authors.affiliation: Department of Oral Biochemistry, Academic Centre for Dentistry Amsterdam, University of Amsterdam and VU University Amsterdam, Gustav Mahlerlaan 3004, 1081LA, Amsterdam, Netherlands.
authors.forename: Antoon J M
authors.initials: AJM
authors.lastname: Ligtenberg
authors.affiliation: Division of Molecular Genome Analysis, German Cancer Research Center, Heidelberg, Germany.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Blaich
authors.affiliation: Division of Molecular Genome Analysis, German Cancer Research Center, Heidelberg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Lyer
authors.affiliation: Division of Molecular Genome Analysis, German Cancer Research Center, Heidelberg, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Renner
authors.affiliation: Division of Molecular Genome Analysis, German Cancer Research Center, Heidelberg, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Wittig
authors.affiliation: Department of Oral Biochemistry, Academic Centre for Dentistry Amsterdam, University of Amsterdam and VU University Amsterdam, Gustav Mahlerlaan 3004, 1081LA, Amsterdam, Netherlands.
authors.forename: Kamran
authors.initials: K
authors.lastname: Nazmi
authors.affiliation: Department of Oral Biochemistry, Academic Centre for Dentistry Amsterdam, University of Amsterdam and VU University Amsterdam, Gustav Mahlerlaan 3004, 1081LA, Amsterdam, Netherlands.
authors.forename: Arie
authors.initials: A
authors.lastname: van Nieuw Amerongen
authors.affiliation: Division of Molecular Genome Analysis, German Cancer Research Center, Heidelberg, Germany.
authors.forename: Annemarie
authors.initials: A
authors.lastname: Poustka
authors.affiliation: Department of Oral Biochemistry, Academic Centre for Dentistry Amsterdam, University of Amsterdam and VU University Amsterdam, Gustav Mahlerlaan 3004, 1081LA, Amsterdam, Netherlands.
authors.forename: Enno C I
authors.initials: ECI
authors.lastname: Veerman
authors.affiliation: Division of Molecular Genome Analysis, German Cancer Research Center, Heidelberg, Germany.|Molecular Oncology, University of Southern Denmark, Odense, Denmark.
authors.forename: Jan
authors.initials: J
authors.lastname: Mollenhauer
mesh_terms: D001422:Bacterial Adhesion / Q000235:genetics; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D018095:Germ-Line Mutation; D006801:Humans; D011110:Polymorphism, Genetic; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D051116:Receptors, Scavenger / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D017384:Sequence Deletion; D025521:Tumor Suppressor Proteins
chemical_list: D002135:Calcium-Binding Proteins; C108174:DMBT1 protein, human; D004268:DNA-Binding Proteins; D011956:Receptors, Cell Surface; D051116:Receptors, Scavenger; D025521:Tumor Suppressor Proteins
keywords: Genetic polymorphism; Microbial defense; Pathogen binding; SRCR domain