3J82

Electron cryo-microscopy of DNGR-1 in complex with F-actin

Summary for 3J82

• Entry DOI: 10.2210/pdb3j82/pdb
• EMDB information: 6102
• Descriptor: C-type lectin domain family 9 member A, Actin, cytoplasmic 1, CALCIUM ION, ... (4 entities in total)
• Functional Keywords: dngr-1, actin, recognition of damage-associated molecular patterns, membrane protein-adp-binding protein complex, membrane protein/adp-binding protein
• Biological source: Mus musculus (mouse); More
• Total number of polymer chains: 4
• Total formula weight: 141284.12

Authors

Hanc, P.,Fujii, T.,Yamada, Y.,Huotari, J.,Schulz, O.,Ahrens, S.,Kjaer, S.,Way, M.,Namba, K.,Reis e Sousa, C. (deposition date: 2014-09-25, release date: 2015-05-20, Last modification date: 2019-12-18)

Primary citation

Hanc, P.,Fujii, T.,Iborra, S.,Yamada, Y.,Huotari, J.,Schulz, O.,Ahrens, S.,Kjer, 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, 42:839-849, 2015

PubMed Abstract: 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 Å 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.

PubMed: 25979418
DOI: 10.1016/j.immuni.2015.04.009

Experimental method

ELECTRON MICROSCOPY (7.7 Å)