8EY8

LaM domain of human LARP1 in complex with AAAAGA RNA

8EY8 の概要

• エントリーDOI: 10.2210/pdb8ey8/pdb
• 関連するPDBエントリー: 7SOW
• 分子名称: Isoform 2 of La-related protein 1, RNA (5'-R(*AP*AP*AP*AP*GP*A)-3') (3 entities in total)
• 機能のキーワード: winged helix fold, rna binding domain, rna binding protein, rna binding protein-rna complex, rna binding protein/rna
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 13752.78

構造登録者

Kozlov, G.,Gehring, K. (登録日: 2022-10-26, 公開日: 2023-11-01, 最終更新日: 2026-03-04)

主引用文献

Kozlov, G.,Jiang, J.,Rutherford, T.,Noronha, A.M.,Wilds, C.J.,Gehring, K.
Enhanced binding of guanylated poly(A) RNA by the LaM domain of LARP1.
Rna Biol., 21:7-16, 2024

PubMed Abstract: La-related proteins (LARPs) are a family of RNA-binding proteins that share a conserved La motif (LaM) domain. LARP1 plays a role in regulating ribosomal protein synthesis and stabilizing mRNAs and has a unique structure without an RNA binding RRM domain adjoining the LaM domain. In this study, we investigated the physical basis for LARP1 specificity for poly(A) sequences and observed an unexpected bias for sequences with single guanines. Multiple guanine substitutions did not increase the affinity, demonstrating preferential recognition of singly guanylated sequences. We also observed that the cyclic di-nucleotides in the cCAS/STING pathway, cyclic-di-GMP and 3',3'-cGAMP, bound with sub-micromolar affinity. Isothermal titration measurements were complemented by high-resolution crystal structures of the LARP1 LaM with six different RNA ligands, including two stereoisomers of a phosphorothioate linkage. The selectivity for singly substituted poly(A) sequences suggests LARP1 may play a role in the stabilizing effect of poly(A) tail guanylation. [Figure: see text].

PubMed: 39016322
DOI: 10.1080/15476286.2024.2379121

実験手法

X-RAY DIFFRACTION (1.3 Å)