A model of full-length RAGE in complex with S100B

被引：13

作者：

Moysa, Alexander ^{[1
]}

Steczkiewicz, Kamil ^{[1
]}

Niedzialek, Dorota ^{[1
]}

Hammerschmid, Dietmar ^{[2
,5
]}

Zhukova, Lilia ^{[1
]}

Sobott, Frank ^{[3
,4
,5
]}

Dadlez, Michal ^{[1
]}

机构：

[1] PAS, Inst Biochem & Biophys, Pawinskiego 5a, PL-02109 Warsaw, Poland

[2] Kings Coll London, Dept Chem, 7 Trinity St, London SE1 1DB, England

[3] Univ Leeds, Astbury Ctr Struct Mol Biol, Woodhouse Lane, Leeds LS2 9JT, W Yorkshire, England

[4] Univ Leeds, Sch Mol & Cellular Biol, Woodhouse Lane, Leeds LS2 9JT, W Yorkshire, England

[5] Univ Antwerp, Dept Chem, Biomol & Analyt Mass Spectrometry Grp, Groenenborgerlaan 171, B-2020 Antwerp, Belgium

来源：

STRUCTURE | 2021年 / 29卷 / 09期

基金：

英国惠康基金;

关键词：

GLYCATION END-PRODUCTS; LINKING MASS-SPECTROMETRY; STRUCTURAL INSIGHTS; HUMAN RECEPTOR; PROTEINS; BINDING; DOMAIN; RECOGNITION; ACTIVATION; MIGRATION;

D O I：

10.1016/j.str.2021.04.002

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The receptor for advanced glycation end products (RAGE) is an immunoglobulin-type multiligand transmembrane protein expressed in numerous cell types, including the central nervous system cells. RAGE interaction with S100B, released during brain tissue damage, leads to RAGE upregulation and initialization of a spiral proinflammatory associated with different neural disorders. Here, we present the structural characterization of the hetero-oligomeric complex of the full-length RAGE with S100B, obtained by a combination of mass spectrometry-based methods and molecular modeling. We predict that RAGE functions as a tightly packed tetramer exposing a positively charged surface formed by V domains for S100B binding. Based on HDX results we demonstrate an allosteric coupling of the distal extracellular V domains and the transmembrane region, indicating a possible mechanism of signal transmission by RAGE across the membrane. Our model provides an insight into RAGE-ligand interactions, providing a basis for the rational design of the therapeutic modifiers of its activity.

引用

页码：989 / +

页数：20

共 80 条

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