2KV4

EGF

2KV4 の概要

• エントリーDOI: 10.2210/pdb2kv4/pdb
• NMR情報: BMRB: 16768
• 分子名称: Epidermal growth factor (1 entity in total)
• 機能のキーワード: epithermal growth factor, egf-like domain, hormone
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 6229.03

構造登録者

Huang, H.W.,Mohan, S.K.,Yu, C. (登録日: 2010-03-08, 公開日: 2011-02-23, 最終更新日: 2024-10-16)

主引用文献

Huang, H.W.,Mohan, S.K.,Yu, C.
The NMR solution structure of human epidermal growth factor (hEGF) at physiological pH and its interactions with suramin
Biochem.Biophys.Res.Commun., 402:705-710, 2010

PubMed Abstract: Human epidermal growth factor (hEGF) induces the proliferation, differentiation and survival of various cell types including tumor-derived cells. Generally, hEGF performs its biological function by binding to a specific receptor (hEGFR) on the cell surface, thereby inducing signal transduction. Suramin, a polysulfonated naphthylurea that acts as a growth factor blocker, exhibits antiproliferative activity against non-small cell lung cancer (NSCLC) cells that overexpress EGFR on the cell surface. We determined the solution structure of hEGF under physiological conditions and investigated the interaction of suramin with hEGF using isothermal titration calorimetry and NMR spectroscopy techniques. The solution structure of hEGF presented in this paper is different from the bound form of hEGF present in the crystal structure of the 2:2 EGF-EGFR complex because its C-tail contains a hydrophobic core. This conformational difference supports the hypothesis that hEGF undergoes a conformational change when it binds to hEGFR and subsequently induces signal transduction. Based on the docking structure of the hEGF-suramin complex, we demonstrated how suramin blocks hEGF by binding to its receptor binding site (the C-terminal region around Arg45) and inhibits the crucial conformational change.

PubMed: 21029725
DOI: 10.1016/j.bbrc.2010.10.089

実験手法

SOLUTION NMR