7L5C

Structure of copper bound MEMO1

7L5C の概要

• エントリーDOI: 10.2210/pdb7l5c/pdb
• 関連するPDBエントリー: 7KQ8
• 分子名称: Protein MEMO1, 1,2-ETHANEDIOL, COPPER (I) ION, ... (5 entities in total)
• 機能のキーワード: metal binding protein, breast cancer, metastasis, cell motility, iron binding protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 135106.45

構造登録者

Boniecki, M.T.,Uhlemann, E.E.,Dmitriev, O.Y. (登録日: 2020-12-21, 公開日: 2022-01-19, 最終更新日: 2024-05-22)

主引用文献

Dolgova, N.,Uhlemann, E.E.,Boniecki, M.T.,Vizeacoumar, F.S.,Ara, A.,Nouri, P.,Ralle, M.,Tonelli, M.,Abbas, S.A.,Patry, J.,Elhasasna, H.,Freywald, A.,Vizeacoumar, F.J.,Dmitriev, O.Y.
MEMO1 binds iron and modulates iron homeostasis in cancer cells.
Elife, 13:-, 2024

PubMed Abstract: Mediator of ERBB2-driven cell motility 1 (MEMO1) is an evolutionary conserved protein implicated in many biological processes; however, its primary molecular function remains unknown. Importantly, MEMO1 is overexpressed in many types of cancer and was shown to modulate breast cancer metastasis through altered cell motility. To better understand the function of MEMO1 in cancer cells, we analyzed genetic interactions of MEMO1 using gene essentiality data from 1028 cancer cell lines and found multiple iron-related genes exhibiting genetic relationships with MEMO1. We experimentally confirmed several interactions between MEMO1 and iron-related proteins in living cells, most notably, transferrin receptor 2 (2), mitoferrin-2 (), and the global iron response regulator IRP1 (). These interactions indicate that cells with high-MEMO1 expression levels are hypersensitive to the disruptions in iron distribution. Our data also indicate that MEMO1 is involved in ferroptosis and is linked to iron supply to mitochondria. We have found that purified MEMO1 binds iron with high affinity under redox conditions mimicking intracellular environment and solved MEMO1 structures in complex with iron and copper. Our work reveals that the iron coordination mode in MEMO1 is very similar to that of iron-containing extradiol dioxygenases, which also display a similar structural fold. We conclude that MEMO1 is an iron-binding protein that modulates iron homeostasis in cancer cells.

PubMed: 38640016
DOI: 10.7554/eLife.86354

実験手法

X-RAY DIFFRACTION (2.55 Å)