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<p>CaMKII predominantly assembles into a 12-meric ring assembly, primarily consisting of α and β isoforms in the brain. Previous biochemical studies reported varying ratios of these CaMKII variants across different brain regions and developmental stages. However, direct evidence for the formation of CaMKIIα/β heterooligomers within a 12-meric ring assembly has been lacking at the single-molecule level. Here, we employ high-speed atomic force microscopy to visualize the conformational dynamics of forebrain-mimicked CaMKIIα/β at a 3:1 ratio. Our findings reveal that the α and β subunits are intermixed within the 12-meric ring assembly, with a probability exceeding 83% that β subunits are positioned adjacently. Furthermore, in the activated state, CaMKIIα/β heterooligomers form a stable kinase domain complex via interactions between adjacent CaMKIIβ subunits, resulting in a long-lasting structure with an exposed target binding site. Collectively, our observations provide insights into the structural role of CaMKIIβ subunits within the CaMKIIα/β heterododecamer.</p>

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Structural dynamics of mixed-subunit CaMKIIα/β heterododecamers filmed by high-speed AFM

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月24日

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  • Keisuke Matsushima,
  • Takashi Sumikama,
  • Taisei Suzuki,
  • Mizuho Ito,
  • Yutaro Nagasawa,
  • Ayumi Sumino,
  • Holger Flechsig,
  • Tomoki Ogoshi,
  • Kenichi Umeda,
  • Noriyuki Kodera,
  • Hideji Murakoshi,
  • Mikihiro Shibata

摘要

CaMKII predominantly assembles into a 12-meric ring assembly, primarily consisting of α and β isoforms in the brain. Previous biochemical studies reported varying ratios of these CaMKII variants across different brain regions and developmental stages. However, direct evidence for the formation of CaMKIIα/β heterooligomers within a 12-meric ring assembly has been lacking at the single-molecule level. Here, we employ high-speed atomic force microscopy to visualize the conformational dynamics of forebrain-mimicked CaMKIIα/β at a 3:1 ratio. Our findings reveal that the α and β subunits are intermixed within the 12-meric ring assembly, with a probability exceeding 83% that β subunits are positioned adjacently. Furthermore, in the activated state, CaMKIIα/β heterooligomers form a stable kinase domain complex via interactions between adjacent CaMKIIβ subunits, resulting in a long-lasting structure with an exposed target binding site. Collectively, our observations provide insights into the structural role of CaMKIIβ subunits within the CaMKIIα/β heterododecamer.