The scavenging capacity of DMBT1 is impaired by germline deletions

Immunogenetics. 2017 Jun;69(6):401-407. doi: 10.1007/s00251-017-0982-x. Epub 2017 Mar 31.

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.

Keywords: Genetic polymorphism; Microbial defense; Pathogen binding; SRCR domain.

MeSH terms

  • Bacterial Adhesion / genetics
  • Calcium-Binding Proteins
  • DNA-Binding Proteins
  • Germ-Line Mutation*
  • Humans
  • Polymorphism, Genetic
  • Protein Binding
  • Protein Interaction Domains and Motifs
  • Receptors, Cell Surface / chemistry
  • Receptors, Cell Surface / genetics*
  • Receptors, Cell Surface / metabolism*
  • Receptors, Scavenger / chemistry
  • Receptors, Scavenger / genetics*
  • Receptors, Scavenger / metabolism*
  • Sequence Deletion*
  • Tumor Suppressor Proteins

Substances

  • Calcium-Binding Proteins
  • DMBT1 protein, human
  • DNA-Binding Proteins
  • Receptors, Cell Surface
  • Receptors, Scavenger
  • Tumor Suppressor Proteins