The
scavenger receptor cysteine-rich (SRCR)
proteins form an archaic group of metazoan
proteins characterized by the presence of SRCR domains. These
proteins are classified in group A and B based on the number of conserved
cysteine residues in their SRCR domains, i.e. six for group A and eight for group B. The
protein DMBT1 (deleted in malignant
brain tumors 1), which is identical to salivary
agglutinin and lung
gp-340, belongs to the group B SRCR
proteins and is considered to be involved in
tumor suppression and host defense by pathogen binding. In a previous study we used nonoverlapping synthetic
peptides covering the SRCR consensus sequence to identify a 16-amino
acid bacteria-
binding protein loop (
peptide SRCRP2; QGRVEVLYRGSWGTVC) within the SRCR domains. In this study, using overlapping
peptides, we pinpointed the minimal bacteria-binding site on SRCRP2, and thus DMBT1, to an 11-amino
acid motif (DMBT1 pathogen-binding site 1 or DMBT1pbs1; GRVEVLYRGSW). An
alanine substitution scan revealed that VEVL and Trp are critical residues in this motif. Bacteria binding by DMBT1pbs1 was different from the bacteria binding by the macrophage receptor MARCO in which an RXR motif was critical. In addition, the homologous consensus sequences of a number of SRCR
proteins were synthesized and tested for bacteria binding. Only consensus sequences of DMBT1 orthologues bound bacteria by this motif.