A pH- and ionic strength-dependent conformational change in the neck region regulates DNGR-1 function in dendritic cells

EMBO J. 2016 Nov 15;35(22):2484-2497. doi: 10.15252/embj.201694695. Epub 2016 Oct 17.


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.

Keywords: C‐type lectin receptors; cross‐presentation; necrosis; protein structure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allosteric Regulation
  • Animals
  • DNA Mutational Analysis
  • Dendritic Cells / metabolism*
  • Hydrogen-Ion Concentration*
  • Lectins, C-Type / chemistry*
  • Lectins, C-Type / genetics
  • Lectins, C-Type / metabolism*
  • Mice
  • Osmolar Concentration*
  • Protein Conformation / drug effects*
  • Receptors, Immunologic / chemistry*
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / metabolism*


  • Clec9a protein, mouse
  • Lectins, C-Type
  • Receptors, Immunologic