Journal
EMBO JOURNAL
Volume 35, Issue 22, Pages 2484-2497Publisher
WILEY
DOI: 10.15252/embj.201694695
Keywords
C-type lectin receptors; cross-presentation; necrosis; protein structure
Categories
Funding
- Francis Crick Institute
- Cancer Research UK [FC001136]
- UK Medical Research Council [FC001136]
- Wellcome Trust [FC001136]
- European Research Council [AdG 268670]
- Cancer Research UK [15689] Funding Source: researchfish
- Medical Research Council [MR/L022699/1] Funding Source: researchfish
- The Francis Crick Institute [10138, 10136] Funding Source: researchfish
- The Francis Crick Institute
- Cancer Research UK [10015] Funding Source: researchfish
- MRC [MR/L022699/1] Funding Source: UKRI
Ask authors/readers for more resources
DNGR-1 is receptor expressed by certain dendritic cell (DC) subsets and by DC precursors in mouse. It possesses a C-type lectin-like domain (CTLD) followed by a poorly characterized neck region coupled to a transmembrane region and short intracellular tail. The CTLD of DNGR-1 binds F-actin exposed by dead cell corpses and causes the receptor to signal and potentiate cross-presentation of dead cell-associated antigens by DCs. Here, we describe a conformational change that occurs in the neck region of DNGR-1 in a pH- and ionic strength-dependent manner and that controls cross-presentation of dead cell-associated antigens. We identify residues in the neck region that, when mutated, lock DNGR-1 in one of the two conformational states to potentiate cross-presentation. In contrast, we show that chimeric proteins in which the neck region of DNGR-1 is replaced by that of unrelated C-type lectin receptors fail to promote cross-presentation. Our results suggest that the neck region of DNGR-1 is an integral receptor component that senses receptor progression through the endocytic pathway and has evolved to maximize extraction of antigens from cell corpses, coupling DNGR-1 function to its cellular localization.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available