5KS5

Structure of the C-terminal Helical Repeat Domain of Elongation Factor 2 Kinase

5KS5 の概要

• エントリーDOI: 10.2210/pdb5ks5/pdb
• NMR情報: BMRB: 30135
• 分子名称: Eukaryotic elongation factor 2 kinase (1 entity in total)
• 機能のキーワード: transferase, eef2k, sel1, elongation, tpr
• 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: 11856.01

構造登録者

Piserchio, A.,Will, N.,Snyder, I.,Ferguson, S.B.,Giles, D.H.,Dalby, K.N.,Ghose, R. (登録日: 2016-07-07, 公開日: 2016-09-14, 最終更新日: 2024-05-15)

主引用文献

Will, N.,Piserchio, A.,Snyder, I.,Ferguson, S.B.,Giles, D.H.,Dalby, K.N.,Ghose, R.
Structure of the C-Terminal Helical Repeat Domain of Eukaryotic Elongation Factor 2 Kinase.
Biochemistry, 55:5377-5386, 2016

PubMed Abstract: Eukaryotic elongation factor 2 kinase (eEF-2K) phosphorylates its only known physiological substrate, elongation factor 2 (eEF-2), which reduces the affinity of eEF-2 for the ribosome and results in an overall reduction in protein translation rates. The C-terminal region of eEF-2K, which is predicted to contain several SEL-1-like helical repeats (SLRs), is required for the phosphorylation of eEF-2. Using solution nuclear magnetic resonance methodology, we have determined the structure of a 99-residue fragment from the extreme C-terminus of eEF-2K (eEF-2K627-725) that encompasses a region previously suggested to be essential for eEF-2 phosphorylation. eEF-2K627-725 contains four helices, of which the first (αI) is flexible, and does not pack stably against the ordered helical core formed by the last three helices (αII-αIV). The helical core is structurally similar to members of the tetratricopeptide repeat (TPR) family that includes SLRs. The two penultimate helices, αII and αIII, comprise the TPR, and the last helix, αIV, appears to have a capping function. The eEF-2K627-725 structure illustrates that the C-terminal deletion that was shown to abolish eEF-2 phosphorylation does so by destabilizing αIV and, therefore, the helical core. Indeed, mutation of two conserved C-terminal tyrosines (Y712A/Y713A) in eEF-2K previously shown to abolish eEF-2 phosphorylation leads to the unfolding of eEF-2K627-725. Preliminary functional analyses indicate that neither a peptide encoding a region deemed crucial for eEF-2 binding nor isolated eEF-2K627-725 inhibits eEF-2 phosphorylation by full-length eEF-2K. Taken together, our data suggest that the extreme C-terminal region of eEF-2K, in isolation, does not provide a primary docking site for eEF-2.

PubMed: 27571275
DOI: 10.1021/acs.biochem.6b00711

実験手法

SOLUTION NMR