4P2Y

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

Summary for 4P2Y

• Entry DOI: 10.2210/pdb4p2y/pdb
• Related: 4LP4 4LP5
• Descriptor: Advanced glycosylation end product-specific receptor, Protein S100-A6, ZINC ION, ... (7 entities in total)
• Functional Keywords: signaling complex, pattern recognition receptor, dimerization, ef-hand calcium binding protein, signaling protein
• Biological source: Homo sapiens (Human); More
• Cellular location: 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 : P14069
• Total number of polymer chains: 2
• Total formula weight: 43971.67

Authors

Yatime, L.,Andersen, G.R. (deposition date: 2014-03-05, release date: 2015-03-11, Last modification date: 2024-10-23)

Primary citation

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, 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

Experimental method

X-RAY DIFFRACTION (2.3 Å)