Molecular Basis of Complement C1q Collagen-Like Region Interaction with the Immunoglobulin-Like Receptor LAIR-1
The immune system homeostasis relies on a tight equilibrium of interconnected stimulatory and inhibitory signals. Disruption of this balance is characteristic of autoimmune diseases such as systemic lupus erythematosus (SLE). Aside from activating the classical complement pathway and enhancing patho...
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MDPI AG
2021-05-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/10/5125 |
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| author | Guillaume Fouët Isabelle Bally Anne Chouquet Jean-Baptiste Reiser Nicole M. Thielens Christine Gaboriaud Véronique Rossi |
| author_facet | Guillaume Fouët Isabelle Bally Anne Chouquet Jean-Baptiste Reiser Nicole M. Thielens Christine Gaboriaud Véronique Rossi |
| author_sort | Guillaume Fouët |
| collection | DOAJ |
| description | The immune system homeostasis relies on a tight equilibrium of interconnected stimulatory and inhibitory signals. Disruption of this balance is characteristic of autoimmune diseases such as systemic lupus erythematosus (SLE). Aside from activating the classical complement pathway and enhancing pathogens and apoptotic cells phagocytosis, C1q has been recently shown to play an important role in immune modulation and tolerance by interacting with several inhibitory and stimulatory immune receptors. Due to its functional organization into collagen-like (CLR) and globular (GR) regions and its multimeric nature, C1q is able to interact simultaneously with several of these receptors and locally congregate pro- and anti-inflammatory signals, thus modulating the immune response. Leukocyte associated immunoglobulin-like (Ig-like) receptor 1 (LAIR-1), a ubiquitous collagen receptor expressed in many immune cell types, has been reported to interact with the CLR of C1q. In this study, we provide new insights into the molecular and structural determinants underlying C1q/LAIR-1 interaction. Recombinant LAIR-1 extracellular Ig-like domain was produced and tested for its interaction with C1q. A molecular dissection of C1q combined with competition assays reveals that LAIR-1 interacts with C1q’s CLR through a binding site close but different from the one of its associated C1r2s2 proteases tetramer. On the other side, we identified LAIR-1 residues involved in C1q interaction by site-directed mutational analysis. All together, these results lead to propose a possible model for C1q interaction with LAIR-1 and will contribute to the fundamental understanding of C1q-mediated immune tolerance. |
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| language | English |
| last_indexed | 2024-03-10T11:29:03Z |
| publishDate | 2021-05-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-b6b1473ea1544ca287ac4f5d3028752e2023-11-21T19:23:50ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-05-012210512510.3390/ijms22105125Molecular Basis of Complement C1q Collagen-Like Region Interaction with the Immunoglobulin-Like Receptor LAIR-1Guillaume Fouët0Isabelle Bally1Anne Chouquet2Jean-Baptiste Reiser3Nicole M. Thielens4Christine Gaboriaud5Véronique Rossi6Institute of Structural Biology (IBS), Univ. Grenoble Alpes, CEA, CNRS, IBS, F-38000 Grenoble, FranceInstitute of Structural Biology (IBS), Univ. Grenoble Alpes, CEA, CNRS, IBS, F-38000 Grenoble, FranceInstitute of Structural Biology (IBS), Univ. Grenoble Alpes, CEA, CNRS, IBS, F-38000 Grenoble, FranceInstitute of Structural Biology (IBS), Univ. Grenoble Alpes, CEA, CNRS, IBS, F-38000 Grenoble, FranceInstitute of Structural Biology (IBS), Univ. Grenoble Alpes, CEA, CNRS, IBS, F-38000 Grenoble, FranceInstitute of Structural Biology (IBS), Univ. Grenoble Alpes, CEA, CNRS, IBS, F-38000 Grenoble, FranceInstitute of Structural Biology (IBS), Univ. Grenoble Alpes, CEA, CNRS, IBS, F-38000 Grenoble, FranceThe immune system homeostasis relies on a tight equilibrium of interconnected stimulatory and inhibitory signals. Disruption of this balance is characteristic of autoimmune diseases such as systemic lupus erythematosus (SLE). Aside from activating the classical complement pathway and enhancing pathogens and apoptotic cells phagocytosis, C1q has been recently shown to play an important role in immune modulation and tolerance by interacting with several inhibitory and stimulatory immune receptors. Due to its functional organization into collagen-like (CLR) and globular (GR) regions and its multimeric nature, C1q is able to interact simultaneously with several of these receptors and locally congregate pro- and anti-inflammatory signals, thus modulating the immune response. Leukocyte associated immunoglobulin-like (Ig-like) receptor 1 (LAIR-1), a ubiquitous collagen receptor expressed in many immune cell types, has been reported to interact with the CLR of C1q. In this study, we provide new insights into the molecular and structural determinants underlying C1q/LAIR-1 interaction. Recombinant LAIR-1 extracellular Ig-like domain was produced and tested for its interaction with C1q. A molecular dissection of C1q combined with competition assays reveals that LAIR-1 interacts with C1q’s CLR through a binding site close but different from the one of its associated C1r2s2 proteases tetramer. On the other side, we identified LAIR-1 residues involved in C1q interaction by site-directed mutational analysis. All together, these results lead to propose a possible model for C1q interaction with LAIR-1 and will contribute to the fundamental understanding of C1q-mediated immune tolerance.https://www.mdpi.com/1422-0067/22/10/5125immune toleranceimmunoglobin-like receptorcomplement C1qcollagen-like region |
| spellingShingle | Guillaume Fouët Isabelle Bally Anne Chouquet Jean-Baptiste Reiser Nicole M. Thielens Christine Gaboriaud Véronique Rossi Molecular Basis of Complement C1q Collagen-Like Region Interaction with the Immunoglobulin-Like Receptor LAIR-1 International Journal of Molecular Sciences immune tolerance immunoglobin-like receptor complement C1q collagen-like region |
| title | Molecular Basis of Complement C1q Collagen-Like Region Interaction with the Immunoglobulin-Like Receptor LAIR-1 |
| title_full | Molecular Basis of Complement C1q Collagen-Like Region Interaction with the Immunoglobulin-Like Receptor LAIR-1 |
| title_fullStr | Molecular Basis of Complement C1q Collagen-Like Region Interaction with the Immunoglobulin-Like Receptor LAIR-1 |
| title_full_unstemmed | Molecular Basis of Complement C1q Collagen-Like Region Interaction with the Immunoglobulin-Like Receptor LAIR-1 |
| title_short | Molecular Basis of Complement C1q Collagen-Like Region Interaction with the Immunoglobulin-Like Receptor LAIR-1 |
| title_sort | molecular basis of complement c1q collagen like region interaction with the immunoglobulin like receptor lair 1 |
| topic | immune tolerance immunoglobin-like receptor complement C1q collagen-like region |
| url | https://www.mdpi.com/1422-0067/22/10/5125 |
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