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Structural basis for collagen recognition by the immune receptor OSCAR

DOI: 10.1182/blood-2015-08-667055 DOI Help
PMID: 26552697 PMID Help

Authors: L. Zhou (University of Cambridge) , J. M. Hinerman (Cincinnati Children's Hospital Medical Center) , M. Blaszczyk (University of Cambridge) , J. L. C. Miller (Cincinnati Children's Hospital Medical Center) , D. G. Conrady (Cincinnati Children's Hospital Medical Center) , A. D. Barrow (Washington University School of Medicine) , D. Y. Chirgadze (University of Cambridge) , D. Bihan (University of Cambridge) , R. W. Farndale (University of Cambridge) , A. B. Herr (Cincinnati Children's Hospital Medical Center)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Blood

State: Published (Approved)
Published: November 2015

Abstract: The Osteoclast-associated receptor (OSCAR) is a collagen-binding immune receptor with important roles in dendritic cell maturation and activation of inflammatory monocytes as well as in osteoclastogenesis. The crystal structure of the OSCAR ectodomain is presented, both free and in complex with a consensus triple-helical peptide (THP). The structures revealed a collagen-binding site in each Ig-like domain (D1 and D2). The THP binds near a hypothetical collagen-binding groove in D1, but a more extensive interaction with D2 is facilitated by the unusually wide D1-D2 inter-domain angle in OSCAR. Direct binding assays, combined with site-directed mutagenesis, confirm that the primary collagen-binding site in OSCAR resides in D2, in marked contrast to the related collagen receptors, GPVI and LAIR-1. Monomeric OSCAR D1D2 binds to the consensus THP with a KD of 28 μM measured in solution, but shows a higher affinity (KD 1.5 μM) when binding to a solid-phase THP, most likely due to an avidity effect. These data suggest a two-stage model for the interaction of OSCAR with a collagen fibril, with transient, low-affinity interactions initiated by the membrane-distal D1, followed by firm adhesion to the primary binding site in D2

Subject Areas: Biology and Bio-materials, Medicine

Instruments: I04-Macromolecular Crystallography

Other Facilities: Advanced Photon Source

Added On: 27/11/2015 11:20

Discipline Tags:

Health & Wellbeing Structural biology Drug Discovery Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)