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

Matsushima, K.; Sumikama, T.; Suzuki, T.; Ito, M.; Nagasawa, Y.; Sumino, A.; Flechsig, H.; Ogoshi, T.; Umeda, K.; Kodera, N.; Murakoshi, H.; Shibata, M.

doi:10.1101/2025.04.24.650392

bioRxiv · 10.1101/2025.04.24.650392

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

Matsushima, K.·Sumikama, T.·Suzuki, T.·Ito, M.·Nagasawa, Y.·Sumino, A.·Flechsig, H.·Ogoshi, T.·Umeda, K.·Kodera, N.·Murakoshi, H.·Shibata, M.

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Abstract

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

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Matsushima, K., Sumikama, T., Suzuki, T., Ito, M., Nagasawa, Y., Sumino, A., Flechsig, H., Ogoshi, T., Umeda, K., Kodera, N., Murakoshi, H., Shibata, M.. 2025-04-26. Structural dynamics of mixed-subunit CaMKIIα/β heterododecamers filmed by high-speed AFM. https://doi.org/10.1101/2025.04.24.650392

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