5V87

Crystal structure of LARP1-unique domain DM15 bound to m7GpppC

5V87 の概要

• エントリーDOI: 10.2210/pdb5v87/pdb
• 関連するPDBエントリー: 5v7c
• 分子名称: La-related protein 1, 7N-METHYL-8-HYDROGUANOSINE-5'-TRIPHOSPHATE, [[(2~{R},3~{S},4~{R},5~{R})-5-(2-azanyl-7-methyl-6-oxidanylidene-1~{H}-purin-9-ium-9-yl)-3,4-bis(oxidanyl)oxolan-2-yl]methoxy-oxidanyl-phosphoryl] [[(2~{R},3~{S},4~{R},5~{R})-5-(4-azanyl-2-oxidanylidene-pyrimidin-1-yl)-3,4-bis(oxidanyl)oxolan-2-yl]methoxy-oxidanyl-phosphoryl] hydrogen phosphate, ... (4 entities in total)
• 機能のキーワード: cap-binding, rna-binding, dm15, 5'top, rna binding protein
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Cytoplasm : Q6PKG0
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 40535.20

構造登録者

Berman, A.J.,Lahr, R.M. (登録日: 2017-03-21, 公開日: 2017-04-19, 最終更新日: 2023-10-04)

主引用文献

Lahr, R.M.,Fonseca, B.D.,Ciotti, G.E.,Al-Ashtal, H.A.,Jia, J.J.,Niklaus, M.R.,Blagden, S.P.,Alain, T.,Berman, A.J.
La-related protein 1 (LARP1) binds the mRNA cap, blocking eIF4F assembly on TOP mRNAs.
Elife, 6:-, 2017

PubMed Abstract: The 5'terminal oligopyrimidine (5'TOP) motif is a -regulatory RNA element located immediately downstream of the 7-methylguanosine [mG] cap of TOP mRNAs, which encode ribosomal proteins and translation factors. In eukaryotes, this motif coordinates the synchronous and stoichiometric expression of the protein components of the translation machinery. La-related protein 1 (LARP1) binds TOP mRNAs, regulating their stability and translation. We present crystal structures of the human LARP1 DM15 region in complex with a 5'TOP motif, a cap analog (mGTP), and a capped cytidine (mGpppC), resolved to 2.6, 1.8 and 1.7 Å, respectively. Our binding, competition, and immunoprecipitation data corroborate and elaborate on the mechanism of 5'TOP motif binding by LARP1. We show that LARP1 directly binds the cap and adjacent 5'TOP motif of TOP mRNAs, effectively impeding access of eIF4E to the cap and preventing eIF4F assembly. Thus, LARP1 is a specialized TOP mRNA cap-binding protein that controls ribosome biogenesis.

PubMed: 28379136
DOI: 10.7554/eLife.24146

実験手法

X-RAY DIFFRACTION (1.692 Å)