4YBH

Crystal structure of the human RAGE ectodomain (VC1C2 fragment) in complex with human S100A6

4YBH の概要

• エントリーDOI: 10.2210/pdb4ybh/pdb
• 関連するPDBエントリー: 4P2Y
• 分子名称: Advanced glycosylation end product-specific receptor, Protein S100-A6, ZINC ION, ... (7 entities in total)
• 機能のキーワード: signaling complex, pattern recognition receptor, dimerization, ef-hand calcium binding protein, immunoglobulin domain, signaling protein
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Isoform 1: Cell membrane; Single-pass type I membrane protein. Isoform 2: Secreted. Isoform 10: Cell membrane ; Single-pass type I membrane protein : Q15109; Nucleus envelope: P06703
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 43894.57

構造登録者

Yatime, L.,Andersen, G.R. (登録日: 2015-02-18, 公開日: 2016-03-02, 最終更新日: 2024-11-13)

主引用文献

Yatime, L.,Betzer, C.,Jensen, R.K.,Mortensen, S.,Jensen, P.H.,Andersen, G.R.
The Structure of the RAGE:S100A6 Complex Reveals a Unique Mode of Homodimerization for S100 Proteins.
Structure, 24:2043-2052, 2016

PubMed 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.

PubMed: 27818100
DOI: 10.1016/j.str.2016.09.011

実験手法

X-RAY DIFFRACTION (2.4 Å)