PMID- 27753620
OWN - NLM
STAT- MEDLINE
DCOM- 20170630
LR  - 20240210
IS  - 1460-2075 (Electronic)
IS  - 0261-4189 (Print)
IS  - 0261-4189 (Linking)
VI  - 35
IP  - 22
DP  - 2016 Nov 15
TI  - A pH- and ionic strength-dependent conformational change in the neck region 
      regulates DNGR-1 function in dendritic cells.
PG  - 2484-2497
AB  - 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.
CI  - (c) 2016 The Authors. Published under the terms of the CC BY 4.0 license.
FAU - Hanc, Pavel
AU  - Hanc P
AD  - Immunobiology Laboratory, The Francis Crick Institute, London, UK.
FAU - Schulz, Oliver
AU  - Schulz O
AD  - Immunobiology Laboratory, The Francis Crick Institute, London, UK.
FAU - Fischbach, Hanna
AU  - Fischbach H
AD  - Immunobiology Laboratory, The Francis Crick Institute, London, UK.
FAU - Martin, Stephen R
AU  - Martin SR
AD  - Structural Biology Science Technology Platform, The Francis Crick Institute, 
      London, UK.
FAU - Kjaer, Svend
AU  - Kjaer S
AD  - Structural Biology Science Technology Platform, The Francis Crick Institute, 
      London, UK.
FAU - Reis e Sousa, Caetano
AU  - Reis e Sousa C
AUID- ORCID: 0000-0001-7392-2119
AD  - Immunobiology Laboratory, The Francis Crick Institute, London, UK 
      caetano@crick.ac.uk.
LA  - eng
GR  - FC001136/CRUK_/Cancer Research UK/United Kingdom
GR  - 15689/CRUK_/Cancer Research UK/United Kingdom
GR  - FC001136/MRC_/Medical Research Council/United Kingdom
GR  - MR/L022699/1/MRC_/Medical Research Council/United Kingdom
GR  - WT_/Wellcome Trust/United Kingdom
GR  - FC001136/WT_/Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20161017
PL  - England
TA  - EMBO J
JT  - The EMBO journal
JID - 8208664
RN  - 0 (Clec9a protein, mouse)
RN  - 0 (Lectins, C-Type)
RN  - 0 (Receptors, Immunologic)
SB  - IM
MH  - Allosteric Regulation
MH  - Animals
MH  - DNA Mutational Analysis
MH  - Dendritic Cells/*metabolism
MH  - *Hydrogen-Ion Concentration
MH  - Lectins, C-Type/*chemistry/genetics/*metabolism
MH  - Mice
MH  - *Osmolar Concentration
MH  - Protein Conformation/*drug effects
MH  - Receptors, Immunologic/*chemistry/genetics/*metabolism
PMC - PMC5109244
OTO - NOTNLM
OT  - C-type lectin receptors
OT  - cross-presentation
OT  - necrosis
OT  - protein structure
EDAT- 2016/11/01 06:00
MHDA- 2017/07/01 06:00
PMCR- 2016/10/17
CRDT- 2016/11/01 06:00
PHST- 2016/05/03 00:00 [received]
PHST- 2016/08/18 00:00 [revised]
PHST- 2016/09/15 00:00 [accepted]
PHST- 2016/11/01 06:00 [pubmed]
PHST- 2017/07/01 06:00 [medline]
PHST- 2016/11/01 06:00 [entrez]
PHST- 2016/10/17 00:00 [pmc-release]
AID - embj.201694695 [pii]
AID - EMBJ201694695 [pii]
AID - 10.15252/embj.201694695 [doi]
PST - ppublish
SO  - EMBO J. 2016 Nov 15;35(22):2484-2497. doi: 10.15252/embj.201694695. Epub 2016 Oct 
      17.