7TY1

Crystal structure of apo eosinophil cationic protein (ribonuclease 3) from Macaca fascicularis (MfECP)

7TY1 の概要

• エントリーDOI: 10.2210/pdb7ty1/pdb
• 分子名称: Eosinophil cationic protein, GLYCEROL, CITRIC ACID, ... (5 entities in total)
• 機能のキーワード: mfecp, rnase 3, ribonuclease, crab-eating macaque, long-tailed macaque, cynomolgus monkey, eosinophil cationic protein, ecp., hydrolase
• 由来する生物種: Macaca fascicularis (crab-eating macaque)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 16971.16

構造登録者

Tran, T.T.Q.,Pham, N.T.H.,Calmettes, C.,Doucet, N. (登録日: 2022-02-11, 公開日: 2023-08-16, 最終更新日: 2024-10-30)

主引用文献

Tran, T.T.Q.,Narayanan, C.,Loes, A.N.,Click, T.H.,Pham, N.T.H.,Letourneau, M.,Harms, M.J.,Calmettes, C.,Agarwal, P.K.,Doucet, N.
Ancestral sequence reconstruction dissects structural and functional differences among eosinophil ribonucleases.
J.Biol.Chem., 300:107280-107280, 2024

PubMed Abstract: Evolutionarily conserved structural folds can give rise to diverse biological functions, yet predicting atomic-scale interactions that contribute to the emergence of novel activities within such folds remains challenging. Pancreatic-type ribonucleases illustrate this complexity, sharing a core structure that has evolved to accommodate varied functions. In this study, we used ancestral sequence reconstruction to probe evolutionary and molecular determinants that distinguish biological activities within eosinophil members of the RNase 2/3 subfamily. Our investigation unveils functional, structural, and dynamical behaviors that differentiate the evolved ancestral ribonuclease (AncRNase) from its contemporary eosinophil RNase orthologs. Leveraging the potential of ancestral reconstruction for protein engineering, we used AncRNase predictions to design a minimal 4-residue variant that transforms human RNase 2 into a chimeric enzyme endowed with the antimicrobial and cytotoxic activities of RNase 3 members. This work provides unique insights into mutational and evolutionary pathways governing structure, function, and conformational states within the eosinophil RNase subfamily, offering potential for targeted modulation of RNase-associated functions.

PubMed: 38588810
DOI: 10.1016/j.jbc.2024.107280

実験手法

X-RAY DIFFRACTION (1.8 Å)