Structural basis for collagen recognition by the immune receptor OSCAR

Area of Science:

• Immunology
• Structural Biology
• Biochemistry

Background:

• Osteoclast-associated receptor (OSCAR) is a collagen-binding immune receptor involved in immune cell function and osteoclastogenesis.
• Understanding OSCAR's collagen-binding mechanism is crucial for its role in immune responses and bone biology.

Purpose of the Study:

• To elucidate the structural basis of OSCAR's collagen binding.
• To characterize the collagen-binding sites within the OSCAR ectodomain.

Main Methods:

• X-ray crystallography to determine the structure of OSCAR ectodomain (free and complexed with peptide).
• Site-directed mutagenesis and direct binding assays (solution and solid-phase) to confirm binding sites and affinities.

Main Results:

• Crystal structures revealed collagen-binding sites in both immunoglobulin-like domains (D1 and D2).
• The primary collagen-binding site was identified in D2, distinct from related receptors.
• OSCAR exhibits a two-stage binding model: transient D1 interaction followed by firm D2 adhesion, with higher affinity on solid-phase via avidity.

Conclusions:

• OSCAR utilizes a unique two-stage mechanism for collagen fibril interaction, initiated by D1 and stabilized by D2.
• Structural insights provide a foundation for understanding OSCAR's function in immune and bone cells.