Structural insights into the oligomerization mode of the human Receptor for Advanced Glycation End-products (RAGE)

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Structural insights into the oligomerization mode of the human Receptor for Advanced Glycation End-products (RAGE). / Yatime, Laure; Andersen, Gregers Rom.

In: F E B S Journal, Vol. 280, No. 24, 12.2013, p. 6556-6568.

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@article{57e2f5b59de544fdab182def24d9f1d0,
title = "Structural insights into the oligomerization mode of the human Receptor for Advanced Glycation End-products (RAGE)",
abstract = "RAGE is a pattern recognition receptor sensing endogenous stress signals associated with the development of various diseases including diabetes, vascular complications, Alzheimer's disease and cancer. RAGE ligands include AGEs, S100 proteins, HMGB1 and amyloid β-peptides/fibrils. Their signaling through RAGE induces a sustained inflammation that accentuates tissue damage, thereby participating in the disease progression. Receptor oligomerization seems to be a crucial parameter for the formation of active signaling complexes although the precise mode of oligomerization remains unclear in the context of these various ligands. Here, we present the first crystal structure of the VC1C2 fragment of the RAGE ectodomain. This structure provides the first description of the C2 domain in the context of the entire ectodomain and supports the observation of its conformational freedom relative to the rigid VC1 domain tandem. In addition, we have obtained a new crystal structure of the RAGE VC1 fragment. The packing in both crystal structures reveals an association of the RAGE molecules through contacts between two V domains and the physiological relevance of this homodimerization mode is discussed. Based on homology with single-pass TM receptors, we also suggest RAGE dimerization through a conserved GxxxG motif within its transmembrane domain. A multimodal homodimerization strategy of RAGE is proposed to form the structural basis for ligand-specific complex formation and signaling functions as well as for RAGE-mediated cell adhesion. This article is protected by copyright. All rights reserved.",
author = "Laure Yatime and Andersen, {Gregers Rom}",
note = "This article is protected by copyright. All rights reserved.",
year = "2013",
month = "12",
doi = "10.1111/febs.12556",
language = "English",
volume = "280",
pages = "6556--6568",
journal = "F E B S Journal",
issn = "1742-464X",
publisher = "Wiley-Blackwell Publishing Ltd.",
number = "24",

}

RIS

TY - JOUR

T1 - Structural insights into the oligomerization mode of the human Receptor for Advanced Glycation End-products (RAGE)

AU - Yatime, Laure

AU - Andersen, Gregers Rom

N1 - This article is protected by copyright. All rights reserved.

PY - 2013/12

Y1 - 2013/12

N2 - RAGE is a pattern recognition receptor sensing endogenous stress signals associated with the development of various diseases including diabetes, vascular complications, Alzheimer's disease and cancer. RAGE ligands include AGEs, S100 proteins, HMGB1 and amyloid β-peptides/fibrils. Their signaling through RAGE induces a sustained inflammation that accentuates tissue damage, thereby participating in the disease progression. Receptor oligomerization seems to be a crucial parameter for the formation of active signaling complexes although the precise mode of oligomerization remains unclear in the context of these various ligands. Here, we present the first crystal structure of the VC1C2 fragment of the RAGE ectodomain. This structure provides the first description of the C2 domain in the context of the entire ectodomain and supports the observation of its conformational freedom relative to the rigid VC1 domain tandem. In addition, we have obtained a new crystal structure of the RAGE VC1 fragment. The packing in both crystal structures reveals an association of the RAGE molecules through contacts between two V domains and the physiological relevance of this homodimerization mode is discussed. Based on homology with single-pass TM receptors, we also suggest RAGE dimerization through a conserved GxxxG motif within its transmembrane domain. A multimodal homodimerization strategy of RAGE is proposed to form the structural basis for ligand-specific complex formation and signaling functions as well as for RAGE-mediated cell adhesion. This article is protected by copyright. All rights reserved.

AB - RAGE is a pattern recognition receptor sensing endogenous stress signals associated with the development of various diseases including diabetes, vascular complications, Alzheimer's disease and cancer. RAGE ligands include AGEs, S100 proteins, HMGB1 and amyloid β-peptides/fibrils. Their signaling through RAGE induces a sustained inflammation that accentuates tissue damage, thereby participating in the disease progression. Receptor oligomerization seems to be a crucial parameter for the formation of active signaling complexes although the precise mode of oligomerization remains unclear in the context of these various ligands. Here, we present the first crystal structure of the VC1C2 fragment of the RAGE ectodomain. This structure provides the first description of the C2 domain in the context of the entire ectodomain and supports the observation of its conformational freedom relative to the rigid VC1 domain tandem. In addition, we have obtained a new crystal structure of the RAGE VC1 fragment. The packing in both crystal structures reveals an association of the RAGE molecules through contacts between two V domains and the physiological relevance of this homodimerization mode is discussed. Based on homology with single-pass TM receptors, we also suggest RAGE dimerization through a conserved GxxxG motif within its transmembrane domain. A multimodal homodimerization strategy of RAGE is proposed to form the structural basis for ligand-specific complex formation and signaling functions as well as for RAGE-mediated cell adhesion. This article is protected by copyright. All rights reserved.

U2 - 10.1111/febs.12556

DO - 10.1111/febs.12556

M3 - Journal article

C2 - 24119142

VL - 280

SP - 6556

EP - 6568

JO - F E B S Journal

JF - F E B S Journal

SN - 1742-464X

IS - 24

ER -