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Immunity. 2015 May 19;42(5):839-849. doi: 10.1016/j.immuni.2015.04.009. Epub 2015 May 12.

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.

Author information

1
Immunobiology Laboratory, The Francis Crick Institute, Lincoln's Inn Fields Laboratory, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.
2
Riken Quantitative Biology Center, 1-3 Yamadaoka, Suita, Osaka 565-0871, Japan.
3
Graduate School of Frontier Biosciences, Osaka University, 1-3 Yamadaoka, Suita, Osaka 565-0871, Japan.
4
Immunobiology of Inflammation Laboratory, Department of Vascular Biology and Inflammation, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.
5
Structural Biology Science Technology Platform, The Francis Crick Institute, Lincoln's Inn Fields Laboratory, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.
6
Cell Motility Laboratory, The Francis Crick Institute, Lincoln's Inn Fields Laboratory, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.
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Contributed equally

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.

PMID:
25979418
PMCID:
PMC5066845
DOI:
10.1016/j.immuni.2015.04.009
[Indexed for MEDLINE]
Free PMC Article

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