The Structure of the RAGE:S100A6 Complex Reveals a Unique Mode of Homodimerization for S100 Proteins

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The Structure of the RAGE:S100A6 Complex Reveals a Unique Mode of Homodimerization for S100 Proteins. / Yatime, Laure; Betzer, Cristine; Jensen, Rasmus Kjeldsen; Mortensen, Sofia; Jensen, Poul Henning; Andersen, Gregers Rom.

I: Structure, Bind 24, Nr. 12, 06.12.2016, s. 2043-2052.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

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@article{2f14daa2e1114167a44800b87ceb993c,
title = "The Structure of the RAGE:S100A6 Complex Reveals a Unique Mode of Homodimerization for S100 Proteins",
abstract = "S100 proteins are calcium-dependent regulators of homeostatic processes. Upon cellular response to stress, and notably during tumorigenesis, they relocalize to the extracellular environment where they induce pro-inflammatory signals by activating the receptor for advanced glycation end products (RAGE), thereby facilitating tumor growth and metastasis. Despite its importance in sustaining inflammation, the structural basis for RAGE-S100 crosstalk is still unknown. Here we report two crystal structures of the RAGE:S100A6 complex encompassing a full-length RAGE ectodomain. The structures, in combination with a comprehensive interaction analysis, suggest that the primary S100A6 binding site is formed by the RAGE C1 domain. Complex formation with S100A6 induces a unique dimeric conformation of RAGE that appears suited for signal transduction and intracellular effector recruitment. Intriguingly, S100A6 adopts a dimeric conformation radically different from all known S100 dimers. We discuss the physiological relevance of this non-canonical homodimeric form in vivo.",
keywords = "Journal Article",
author = "Laure Yatime and Cristine Betzer and Jensen, {Rasmus Kjeldsen} and Sofia Mortensen and Jensen, {Poul Henning} and Andersen, {Gregers Rom}",
note = "Copyright {\^A}{\textcopyright} 2016 Elsevier Ltd. All rights reserved.",
year = "2016",
month = dec,
day = "6",
doi = "10.1016/j.str.2016.09.011",
language = "English",
volume = "24",
pages = "2043--2052",
journal = "Structure",
issn = "0969-2126",
publisher = "Cell Press",
number = "12",

}

RIS

TY - JOUR

T1 - The Structure of the RAGE:S100A6 Complex Reveals a Unique Mode of Homodimerization for S100 Proteins

AU - Yatime, Laure

AU - Betzer, Cristine

AU - Jensen, Rasmus Kjeldsen

AU - Mortensen, Sofia

AU - Jensen, Poul Henning

AU - Andersen, Gregers Rom

N1 - Copyright © 2016 Elsevier Ltd. All rights reserved.

PY - 2016/12/6

Y1 - 2016/12/6

N2 - S100 proteins are calcium-dependent regulators of homeostatic processes. Upon cellular response to stress, and notably during tumorigenesis, they relocalize to the extracellular environment where they induce pro-inflammatory signals by activating the receptor for advanced glycation end products (RAGE), thereby facilitating tumor growth and metastasis. Despite its importance in sustaining inflammation, the structural basis for RAGE-S100 crosstalk is still unknown. Here we report two crystal structures of the RAGE:S100A6 complex encompassing a full-length RAGE ectodomain. The structures, in combination with a comprehensive interaction analysis, suggest that the primary S100A6 binding site is formed by the RAGE C1 domain. Complex formation with S100A6 induces a unique dimeric conformation of RAGE that appears suited for signal transduction and intracellular effector recruitment. Intriguingly, S100A6 adopts a dimeric conformation radically different from all known S100 dimers. We discuss the physiological relevance of this non-canonical homodimeric form in vivo.

AB - S100 proteins are calcium-dependent regulators of homeostatic processes. Upon cellular response to stress, and notably during tumorigenesis, they relocalize to the extracellular environment where they induce pro-inflammatory signals by activating the receptor for advanced glycation end products (RAGE), thereby facilitating tumor growth and metastasis. Despite its importance in sustaining inflammation, the structural basis for RAGE-S100 crosstalk is still unknown. Here we report two crystal structures of the RAGE:S100A6 complex encompassing a full-length RAGE ectodomain. The structures, in combination with a comprehensive interaction analysis, suggest that the primary S100A6 binding site is formed by the RAGE C1 domain. Complex formation with S100A6 induces a unique dimeric conformation of RAGE that appears suited for signal transduction and intracellular effector recruitment. Intriguingly, S100A6 adopts a dimeric conformation radically different from all known S100 dimers. We discuss the physiological relevance of this non-canonical homodimeric form in vivo.

KW - Journal Article

U2 - 10.1016/j.str.2016.09.011

DO - 10.1016/j.str.2016.09.011

M3 - Journal article

C2 - 27818100

VL - 24

SP - 2043

EP - 2052

JO - Structure

JF - Structure

SN - 0969-2126

IS - 12

ER -