| Structural highlights
Function
CLC9A_MOUSE Functions as an endocytic receptor on a small subset of myeloid cells specialized for the uptake and processing of material from dead cells. Recognizes filamentous form of actin in association with particular actin-binding domains of cytoskeletal proteins, including spectrin, exposed when cell membranes are damaged, and mediate the cross-presentation of dead-cell associated antigens in a Syk-dependent manner.[1] [2] [3] [4]
Publication Abstract from PubMed
DNGR-1 is a C-type lectin receptor that binds F-actin exposed by dying cells and facilitates cross-presentation of dead cell-associated antigens by dendritic cells. Here we present the structure of DNGR-1 bound to F-actin at 7.7 A resolution. Unusually for F-actin binding proteins, the DNGR-1 ligand binding domain contacts three actin subunits helically arranged in the actin filament, bridging over two protofilaments, as well as two neighboring actin subunits along one protofilament. Mutation of residues predicted to mediate ligand binding led to loss of DNGR-1-dependent cross-presentation of dead cell-associated antigens, formally demonstrating that the latter depends on F-actin recognition. Notably, DNGR-1 has relatively modest affinity for F-actin but multivalent interactions allow a marked increase in binding strength. Our findings shed light on modes of actin binding by cellular proteins and reveal how extracellular detection of cytoskeletal components by dedicated receptors allows immune monitoring of loss of cellular integrity.
Structure of the Complex of F-Actin and DNGR-1, a C-Type Lectin Receptor Involved in Dendritic Cell Cross-Presentation of Dead Cell-Associated Antigens.,Hanc P, Fujii T, Iborra S, Yamada Y, Huotari J, Schulz O, Ahrens S, Kjaer S, Way M, Sancho D, Namba K, Reis e Sousa C Immunity. 2015 May 19;42(5):839-849. doi: 10.1016/j.immuni.2015.04.009. Epub 2015, May 12. PMID:25979418[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Huysamen C, Willment JA, Dennehy KM, Brown GD. CLEC9A is a novel activation C-type lectin-like receptor expressed on BDCA3+ dendritic cells and a subset of monocytes. J Biol Chem. 2008 Jun 13;283(24):16693-701. Epub 2008 Apr 11. PMID:18408006 doi:http://dx.doi.org/M709923200
- ↑ Sancho D, Mourao-Sa D, Joffre OP, Schulz O, Rogers NC, Pennington DJ, Carlyle JR, Reis e Sousa C. Tumor therapy in mice via antigen targeting to a novel, DC-restricted C-type lectin. J Clin Invest. 2008 Jun;118(6):2098-110. doi: 10.1172/JCI34584. PMID:18497879 doi:10.1172/JCI34584
- ↑ Sancho D, Joffre OP, Keller AM, Rogers NC, Martinez D, Hernanz-Falcon P, Rosewell I, Reis e Sousa C. Identification of a dendritic cell receptor that couples sensing of necrosis to immunity. Nature. 2009 Apr 16;458(7240):899-903. doi: 10.1038/nature07750. PMID:19219027 doi:10.1038/nature07750
- ↑ Zhang JG, Czabotar PE, Policheni AN, Caminschi I, San Wan S, Kitsoulis S, Tullett KM, Robin AY, Brammananth R, van Delft MF, Lu J, O'Reilly LA, Josefsson EC, Kile BT, Chin WJ, Mintern JD, Olshina MA, Wong W, Baum J, Wright MD, Huang DC, Mohandas N, Coppel RL, Colman PM, Nicola NA, Shortman K, Lahoud MH. The Dendritic Cell Receptor Clec9A Binds Damaged Cells via Exposed Actin Filaments. Immunity. 2012 Apr 20;36(4):646-57. Epub 2012 Apr 5. PMID:22483802 doi:10.1016/j.immuni.2012.03.009
- ↑ Hanc P, Fujii T, Iborra S, Yamada Y, Huotari J, Schulz O, Ahrens S, Kjaer S, Way M, Sancho D, Namba K, Reis e Sousa C. Structure of the Complex of F-Actin and DNGR-1, a C-Type Lectin Receptor Involved in Dendritic Cell Cross-Presentation of Dead Cell-Associated Antigens. Immunity. 2015 May 19;42(5):839-849. doi: 10.1016/j.immuni.2015.04.009. Epub 2015, May 12. PMID:25979418 doi:http://dx.doi.org/10.1016/j.immuni.2015.04.009
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