4B6V

The third member of the eIF4E family represses gene expression via a novel mode of recognition of the methyl-7 guanosine cap moiety

4B6V の概要

• エントリーDOI: 10.2210/pdb4b6v/pdb
• 関連するPDBエントリー: 4B6U
• NMR情報: BMRB: 18663
• 分子名称: EUKARYOTIC TRANSLATION INITIATION FACTOR 4E TYPE 3 (1 entity in total)
• 機能のキーワード: translation, m7g cap
• 由来する生物種: MUS MUSCULUS (HOUSE MOUSE)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 22864.07

構造登録者

Osborne, M.J.,Volpon, L.,Kornblatt, J.A.,Culjkovic-Kraljcic, B.,Baguet, A.,Borden, K.L.B. (登録日: 2012-08-15, 公開日: 2013-02-27, 最終更新日: 2024-06-19)

主引用文献

Osborne, M.J.,Volpon, L.,Kornblatt, J.A.,Culjkovic-Kraljacic, B.,Baguet, A.,Borden, K.L.B.
Eif4E3 Acts as a Tumor Suppressor by Utilizing an Atypical Mode of Methyl-7-Guanosine CAP Recognition.
Proc.Natl.Acad.Sci.USA, 110:3877-, 2013

PubMed Abstract: Recognition of the methyl-7-guanosine (m(7)G) cap structure on mRNA is an essential feature of mRNA metabolism and thus gene expression. Eukaryotic translation initiation factor 4E (eIF4E) promotes translation, mRNA export, proliferation, and oncogenic transformation dependent on this cap-binding activity. eIF4E-cap recognition is mediated via complementary charge interactions of the positively charged m(7)G cap between the negative π-electron clouds from two aromatic residues. Here, we demonstrate that a variant subfamily, eIF4E3, specifically binds the m(7)G cap in the absence of an aromatic sandwich, using instead a different spatial arrangement of residues to provide the necessary electrostatic and van der Waals contacts. Contacts are much more extensive between eIF4E3-cap than other family members. Structural analyses of other cap-binding proteins indicate this recognition mode is atypical. We demonstrate that eIF4E3 relies on this cap-binding activity to act as a tumor suppressor, competing with the growth-promoting functions of eIF4E. In fact, reduced eIF4E3 in high eIF4E cancers suggests that eIF4E3 underlies a clinically relevant inhibitory mechanism that is lost in some malignancies. Taken together, there is more structural plasticity in cap recognition than previously thought, and this is physiologically relevant.

PubMed: 23431134
DOI: 10.1073/PNAS.1216862110

実験手法

SOLUTION NMR