期刊
CELL REPORTS
卷 37, 期 13, 页码 -出版社
CELL PRESS
DOI: 10.1016/j.celrep.2021.110168
关键词
-
类别
资金
- National Institutes of Health [F32AG066536, P30NS048154, R01NS081248, R01NS118786, R35GM124779, R01EY030987]
By utilizing single-particle electron microscopy, a comparative analysis of neuronal CaMKII holoenzymes' alpha and beta isoforms was conducted, revealing different assembly states in the basal condition. The study also suggests that the beta isoform of CaMKII adopts a larger extended state, allowing for direct resolution of intra-holoenzyme kinase domain dimers.
Neuronal CaMKII holoenzymes (alpha and beta isoforms) enable molecular signal computation underlying learning and memory but also mediate excitotoxic neuronal death, Here, we provide a comparative analysis of these signaling devices, using single-particle electron microscopy (EM) in combination with biochemical and livecell imaging studies. In the basal state, both isoforms assemble mainly as 12-mers (but also 14-mers and even 16-mers for the beta isoform). CaMKII alpha and beta isoforms adopt an ensemble of extended activatable states (with average radius of 12.6 versus 16.8 nm, respectively), characterized by multiple transient intra- and interholoenzyme interactions associated with distinct functional properties. The extended state of CaMKII beta allows direct resolution of intra-holoenzyme kinase domain dimers. These dimers could enable cooperative activation by calmodulin, which is observed for both isoforms. High-order CaMKII clustering mediated by inter-holoenzyme kinase domain dimerization is reduced for the isoform for both basal and excitotoxicity-induced clusters, both in vitro and in neurons.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据