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

ABSTRACT: 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.

SUBMITTER: Hanc P

PROVIDER: S-EPMC5109244 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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

Hanč Pavel P Schulz Oliver O Fischbach Hanna H Martin Stephen R SR Kjær Svend S Reis e Sousa Caetano C

The EMBO journal 20161017 22

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 regio ...[more]

PMID: 27753620

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Dataset Information

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

Publications

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

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