Arginine residues in domain V have a central role for bacteria-binding activity of macrophage scavenger receptor MARCO.
MARCO is a bacteria-binding macrophage-specific scavenger receptor that plays a role in innate immune response. MARCO has short intracellular and transmembrane domains, as well as a large extracellular domain composed of a spacer domain, a long collagenous domain, and a C-terminal scavenger receptor cysteine-rich domain (SRCR), domain V. As yet, no specific function has been assigned to the SRCR domain of scavenger receptors. In the present study, we generated several human and mouse MARCO variants with deletions or single amino acid substitutions and localized the primary bacteria-binding region to domain V. Furthermore, analysis of the MARCO variants containing only portions of domain V demonstrated a crucial role for an arginine-rich segment for this function. More precisely, the motif RXR was identified as an essential element for high-affinity bacterial binding. The results indicate that the binding properties of MARCO differ from those of the other class A scavenger receptors, SR-A and SRCL, whose ligand-binding function has been localized to the collagenous domain.
Brännström
Annika
A
Division of Matrix Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, S-171 77, Sweden.
Sankala
Marko
M
Tryggvason
Karl
K
Pikkarainen
Timo
T
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D001120:Arginine / Q000235:genetics / Q000502:physiology*; D001422:Bacterial Adhesion / Q000235:genetics; D016466:CHO Cells; D006224:Cricetinae; D004926:Escherichia coli / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008264:Macrophages / Q000378:metabolism* / Q000382:microbiology; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010446:Peptide Fragments / Q000235:genetics / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000235:genetics / Q000502:physiology; D011971:Receptors, Immunologic / Q000235:genetics / Q000502:physiology*; D014162:Transfection
C490460:MARCO protein, human; C092228:Marco protein, mouse; D010446:Peptide Fragments; D011971:Receptors, Immunologic; D001120:Arginine