Structural basis for collagen recognition by the immune receptor OSCAR

Zhou, Long; Hinerman, Jennifer M.; Błaszczyk, M.; Miller, Jeanette L.C.; Conrady, Deborah G.; Barrow, Alexander D.; Chirgadze, Dimitri Y.; Bihan, Dominique; Farndale, Richard W.; Herr, Andrew B.

doi:10.1182/blood-2015-08-667055

Cited by 46 publications

(63 citation statements)

References 31 publications

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“…One might speculate that these properties would maintain access of osteoclasts and their precursors to the nearby OSCAR motifs in collagen II, GAOGPQGFQ in D1 and the collagen II-specific GAOGASGDR motif [38], [39] in D5, to promote its resorption, or might allow access of regulatory species such as decorin or fibromodulin [40] to their binding sites near the KGHR fibre-crosslinking locus in D1 and D4. Access of bone-forming cells to both sites in the nascent collagens I and III might be crucial as maturing cartilage is resorbed and replaced by bone during endochondral ossification and skeletal development.…”

Section: Discussionmentioning

confidence: 99%

Unique charge-dependent constraint on collagen recognition by integrin α10β1

et al. 2017

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The collagen-binding integrins recognise collagen through their inserted (I) domain, where co-ordination of a Mg2 + ion in the metal ion-dependent site is reorganised by ligation by a collagen glutamate residue found in specific collagen hexapeptide motifs. Here we show that GROGER, found in the N-terminal domain of collagens I and III, is only weakly recognised by α10β1, an important collagen receptor on chondrocytes, contrasting with the other collagen-binding integrins. Alignment of I domain sequence and molecular modelling revealed a clash between a unique arginine residue (R215) in α10β1 and the positively-charged GROGER. Replacement of R215 with glutamine restored binding. Substituting arginine at the equivalent locus (Q214) in integrins α1 and α2 I domains impaired their binding to GROGER. Collagen II, abundant in cartilage, lacks GROGER. GRSGET is uniquely expressed in the C-terminus of collagen II, but this motif is similarly not recognised by α10β1. These data suggest an evolutionary imperative to maintain accessibility of the terminal domains of collagen II in tissues such as cartilage, perhaps during endochondral ossification, where α10β1 is the main collagen-binding integrin.

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Section: Discussionmentioning

confidence: 99%

Unique charge-dependent constraint on collagen recognition by integrin α10β1

et al. 2017

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“…Of interest, collagen has been recently demonstrated to act as a ligand for a number of stimulatory and inhibitory receptors in this family, including osteoclast associated receptor (OSCAR), GPVI, and LAIR-1 [21][22][23]. The structural basis for collagen recognition by the immune receptors has been investigated in a number of studies [24][25][26][27], however some controversy regarding the alignment of collagen-recognition sites among different receptors exists.…”

Section: Leukocyte Receptor Complex (Lrc)mentioning

confidence: 99%

“…OSCAR is particularly important for osteoclast differentiation, as it acts as a critical co-stimulatory receptor for osteoclast formation and function [23,[26][27][28]. GPVI is mainly found in platelets and binds to collagen during the process of blood coagulation [21].…”

Section: Leukocyte Receptor Complex (Lrc)mentioning

confidence: 99%

Collagen Type I as a Ligand for Receptor-Mediated Signaling

et al. 2017

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Collagens form the fibrous component of the extracellular matrix in all multi-cellular animals. Collagen type I is the most abundant collagen present in skin, tendons, vasculature, as well as the organic portion of the calcified tissue of bone and teeth. This review focuses on numerous receptors for which collagen acts as a ligand, including integrins, discoidin domain receptors DDR1 and 2, OSCAR, GPVI, G6b-B, and LAIR-1 of the leukocyte receptor complex (LRC) and mannose family receptor uPARAP/Endo180. We explore the process of collagen production and self-assembly, as well as its degradation by collagenases and gelatinases in order to predict potential temporal and spatial sites of action of different collagen receptors. While the interactions of the mature collagen matrix with integrins and DDR are well-appreciated, potential signals from immature matrix as well as collagen degradation products are possible but not yet described. The role of multiple collagen receptors in physiological processes and their contribution to pathophysiology of diseases affecting collagen homeostasis require further studies.

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“…Similar to GPVI receptors, OSCAR expression and downstream signaling is stabilized by the adaptor protein FCRγ (Merck et al 2004). OSCAR binds fibrillar type I-III collagens through the consensus motif GPOGPAGFO (Barrow et al 2011;Zhou et al 2016). OSCAR is expressed by osteoclasts, vascular endothelial cells, macrophages, neutrophils, monocytes, and dendritic cells (Kim et al 2002;Koga et al 2004).…”

Section: Oscarmentioning

confidence: 98%

Contribution of collagen adhesion receptors to tissue fibrosis

Coelho

McCulloch

2016

Cell Tissue Res

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Fibrosis is the result of a wound-healing response that fails to restore normal tissue structure function. One of the critical hallmarks of fibrosis is disrupted collagen remodeling. In tissue homeostasis, the production, deposition and organization of collagen is balanced by the degradation and remodeling of collagen within the existing matrix. After injury or chronic infection, tissues initiate a wound-healing response that is intended to create a new ECM for restoring tissue structure and function. If the wound-healing response is dysregulated or if the tissue injury or infection is severe or long-lasting, collagen deposition exceeds collagen degradation and the tissue repair process leads to fibrosis. The fibrotic repair response is extraordinarily complex and involves a wide spectrum of cells, signaling pathways and regulatory systems, some of which can be readily disrupted and thereby contribute to fibrotic lesions. The dysregulated collagen remodeling is a common end-point of all fibrotic disorders, and one of the rate-limiting steps of collagen remodeling is the binding of cells to collagen fibrils by specific cell adhesion receptors. In this review, we describe how the expression and function of collagen adhesion receptors contribute to collagen processing events that contribute to tissue fibrosis. Graphical abstract Balance between collagen remodeling in health and disease.

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Structural basis for collagen recognition by the immune receptor OSCAR

Cited by 46 publications

References 31 publications

Unique charge-dependent constraint on collagen recognition by integrin α10β1

Unique charge-dependent constraint on collagen recognition by integrin α10β1

Collagen Type I as a Ligand for Receptor-Mediated Signaling

Contribution of collagen adhesion receptors to tissue fibrosis

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