Structural dynamics of mixed-subunit CaMKIIα/β heterododecamers filmed by high-speed AFM
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.
Authors
- Taisei Suzuki (ORCID: https://orcid.org/0009-0002-4708-4136)
- Kenichi Umeda (ORCID: https://orcid.org/0000-0002-3650-3828)
- Tomoki Ogoshi (ORCID: https://orcid.org/0000-0002-4464-0347)
- Takashi Sumikama (ORCID: https://orcid.org/0000-0003-3696-5720)
- Keisuke Matsushima
- Noriyuki Kodera (ORCID: https://orcid.org/0000-0003-4880-8423)
- Holger Flechsig (ORCID: https://orcid.org/0000-0003-4984-9294)
- Yutaro Nagasawa (ORCID: https://orcid.org/0000-0002-7471-268X)
- Hideji Murakoshi
- Ayumi Sumino
- Mizuho Ito
- Mikihiro Shibata
Institutions
- Kanazawa University (JP)
- The Graduate University for Advanced Studies, SOKENDAI (JP)
- Kyoto University (JP)
- Life Science Institute (JP)
- National Institute for Physiological Sciences (JP)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-12-24
- DOI
- https://doi.org/10.1038/s41467-025-66527-9
- Citations
- 1
- Primary Topic
- Protein Kinase Regulation and GTPase Signaling
- Type
- article
- Field-Weighted Citation Impact
- 0.81
Funders
- Kanazawa University
- Ministry of Education, Culture, Sports, Science and Technology
- Mochida Memorial Foundation for Medical and Pharmaceutical Research
- Japan Society for the Promotion of Science
- Core Research for Evolutional Science and Technology
- Exploratory Research for Advanced Technology