6NX4

Structure of the C-terminal Helical Repeat Domain of Eukaryotic Elongation Factor 2 Kinase (eEF-2K)

6NX4 の概要

• エントリーDOI: 10.2210/pdb6nx4/pdb
• NMR情報: BMRB: 30569
• 分子名称: Eukaryotic elongation factor 2 kinase (1 entity in total)
• 機能のキーワード: eef2k, eef2, binding domain, kinase, transferase, sel1, elongation, tpr, translation
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 18893.02

構造登録者

Piserchio, A.,Will, N.,Giles, D.H.,Hajredini, F.,Dalby, K.N.,Ghose, R. (登録日: 2019-02-08, 公開日: 2019-05-29, 最終更新日: 2024-05-01)

主引用文献

Piserchio, A.,Will, N.,Giles, D.H.,Hajredini, F.,Dalby, K.N.,Ghose, R.
Solution Structure of the Carboxy-Terminal Tandem Repeat Domain of Eukaryotic Elongation Factor 2 Kinase and Its Role in Substrate Recognition.
J.Mol.Biol., 431:2700-2717, 2019

PubMed Abstract: Eukaryotic elongation factor 2 kinase (eEF-2K), an atypical calmodulin-activated protein kinase, regulates translational elongation by phosphorylating its substrate, eukaryotic elongation factor 2 (eEF-2), thereby reducing its affinity for the ribosome. The activation and activity of eEF-2K are critical for survival under energy-deprived conditions and is implicated in a variety of essential physiological processes. Previous biochemical experiments have indicated that the binding site for the substrate eEF-2 is located in the C-terminal domain of eEF-2K, a region predicted to harbor several α-helical repeats. Here, using NMR methodology, we have determined the solution structure of a C-terminal fragment of eEF-2K, eEF-2K that encodes two α-helical repeats. The structure of eEF-2K shows signatures characteristic of TPR domains and of their SEL1-like sub-family. Furthermore, using the analyses of NMR spectral perturbations and ITC measurements, we have localized the eEF-2 binding site on eEF-2K. We find that eEF-2K engages eEF-2 with an affinity comparable to that of the full-length enzyme. Furthermore, eEF-2K is able to inhibit the phosphorylation of eEF-2 by full-length eEF-2K in trans. Our present studies establish that eEF-2K encodes the major elements necessary to enable the eEF-2K/eEF-2 interactions.

PubMed: 31108082
DOI: 10.1016/j.jmb.2019.05.019

実験手法

SOLUTION NMR