8T17

Cryo-EM structure of tetradecameric hub domain of CaMKII beta

8T17 の概要

• エントリーDOI: 10.2210/pdb8t17/pdb
• 関連するPDBエントリー: 8syg
• EMDBエントリー: 40873 40956
• 分子名称: Venus-tagged CaMKII Beta Association Domain (1 entity in total)
• 機能のキーワード: high-order oligomer, protein kinase, signaling, memory, signaling protein
• 由来する生物種: Aequorea victoria; 詳細
• タンパク質・核酸の鎖数: 14
• 化学式量合計: 638807.97

構造登録者

Chien, C.-T.,Chiu, W.,Khan, S. (登録日: 2023-06-02, 公開日: 2024-06-12, 最終更新日: 2024-07-10)

主引用文献

Chien, C.T.,Puhl, H.,Vogel, S.S.,Molloy, J.E.,Chiu, W.,Khan, S.
Hub stability in the calcium calmodulin-dependent protein kinase II.
Commun Biol, 7:766-766, 2024

PubMed Abstract: The calcium calmodulin protein kinase II (CaMKII) is a multi-subunit ring assembly with a central hub formed by the association domains. There is evidence for hub polymorphism between and within CaMKII isoforms, but the link between polymorphism and subunit exchange has not been resolved. Here, we present near-atomic resolution cryogenic electron microscopy (cryo-EM) structures revealing that hubs from the α and β isoforms, either standalone or within an β holoenzyme, coexist as 12 and 14 subunit assemblies. Single-molecule fluorescence microscopy of Venus-tagged holoenzymes detects intermediate assemblies and progressive dimer loss due to intrinsic holoenzyme lability, and holoenzyme disassembly into dimers upon mutagenesis of a conserved inter-domain contact. Molecular dynamics (MD) simulations show the flexibility of 4-subunit precursors, extracted in-silico from the β hub polymorphs, encompassing the curvature of both polymorphs. The MD explains how an open hub structure also obtained from the β holoenzyme sample could be created by dimer loss and analysis of its cryo-EM dataset reveals how the gap could open further. An assembly model, considering dimer concentration dependence and strain differences between polymorphs, proposes a mechanism for intrinsic hub lability to fine-tune the stoichiometry of αβ heterooligomers for their dynamic localization within synapses in neurons.

PubMed: 38918547
DOI: 10.1038/s42003-024-06423-y

実験手法

ELECTRON MICROSCOPY (2.6 Å)