5L7M

Murin CXCL13 solution structure

5L7M の概要

• エントリーDOI: 10.2210/pdb5l7m/pdb
• NMR情報: BMRB: 34005
• 分子名称: C-X-C motif chemokine 13 (1 entity in total)
• 機能のキーワード: chemokine structure, n-terminal domain, signaling protein, gag binding
• 由来する生物種: Mus musculus (Mouse)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 9807.67

構造登録者

Monneau, Y.R.,Lortat-Jacob, H. (登録日: 2016-06-03, 公開日: 2017-06-21, 最終更新日: 2024-11-13)

主引用文献

Monneau, Y.R.,Luo, L.,Sankaranarayanan, N.V.,Nagarajan, B.,Vives, R.R.,Baleux, F.,Desai, U.R.,Arenzana-Seidedos, F.,Lortat-Jacob, H.
Solution structure of CXCL13 and heparan sulfate binding show that GAG binding site and cellular signalling rely on distinct domains.
Open Biol, 7:-, 2017

PubMed Abstract: Chemokines promote directional cell migration through binding to G-protein-coupled receptors, and as such are involved in a large array of developmental, homeostatic and pathological processes. They also interact with heparan sulfate (HS), the functional consequences of which depend on the respective location of the receptor- and the HS-binding sites, a detail that remains elusive for most chemokines. Here, to set up a biochemical framework to investigate how HS can regulate CXCL13 activity, we solved the solution structure of CXCL13. We showed that it comprises an unusually long and disordered C-terminal domain, appended to a classical chemokine-like structure. Using three independent experimental approaches, we found that it displays a unique association mode to HS, involving two clusters located in the α-helix and the C-terminal domain. Computational approaches were used to analyse the HS sequences preferentially recognized by the protein and gain atomic-level understanding of the CXCL13 dimerization induced upon HS binding. Starting with four sets of 254 HS tetrasaccharides, we identified 25 sequences that bind to CXCL13 monomer, among which a single one bound to CXCL13 dimer with high consistency. Importantly, we found that CXCL13 can be functionally presented to its receptor in a HS-bound form, suggesting that it can promote adhesion-dependent cell migration. Consistently, we designed CXCL13 mutations that preclude interaction with HS without affecting CXCR5-dependent cell signalling, opening the possibility to unambiguously demonstrate the role of HS in the biological function of this chemokine.

PubMed: 29070611
DOI: 10.1098/rsob.170133

実験手法

SOLUTION NMR