Crystal structure of human CaMKII holoenzyme in autoinhibited conformation reveals compact arrangement of kinase domains docked against central hub with calmodulin-binding sites inaccessible. Linker length varies across isoforms and tunes frequency sensitivity. This is the correct CaMKII structural/kinetic reference for h05 — NOT PMID 21458670 (which is Edlich et al. 2011 on Bcl-xL/Bax, an apoptosis paper with no CaMKII content). The “Chao 2011 Cell PMID 21458670” attribution is a phantom citation — PMID 21458670 resolves to a different paper entirely.
Key finding
EC50 for CaM-dependent activation of short-linker CaMKII = 6.0 µM with Hill coefficient n~2.1. I321E mutation reduces EC50 to ~30 nM (non-cooperative). Long-linker isoforms show lower EC50 (nM range) with n=1.4–2.4. Autoinhibition strength is linker-length-tunable, explaining isoform-specific frequency response. This paper is structural; explicit rate constants for autophosphorylation (k_auto) are NOT reported.
Numbers that matter
| Parameter | Value | Units | Conditions | Notes |
|---|---|---|---|---|
| CaM EC50 (short linker, WT) | 6.0 | µM | Human CaMKIIα holoenzyme | Full-length dodecamer, FRET assay |
| Hill coefficient n (short linker) | 2.1 | — | — | Cooperative activation |
| CaM EC50 (I321E mutant) | ~30 | nM | — | Disrupted autoinhibition |
| Hill coefficient n (I321E) | ~1.0 | — | — | Non-cooperative |
| k_auto (/s) | NOT REPORTED | — | — | This paper does not measure autophosphorylation rate |
| Kd_CaMKII | NOT DIRECTLY GIVEN | — | — | EC50 ~6 µM for activation; Kd for binding may differ |
Model implications: h05 uses Kd_CaMKII = 1 µM (order-of-magnitude estimate). Chao 2011 gives EC50 = 6 µM for full holoenzyme activation — the h05 value is ~6× lower. The 1 µM figure is plausible as a lower-bound estimate but is not directly measured in this paper.
Limitations
- EC50 measured for the short-linker isoform specifically; cochlear OHC CaMKII isoform identity is not established.
- Structural paper; k_auto and k_dephos are not measured here.
- PMID 21458670 (the citation used in h05 scripts prior to audit) is NOT this paper — it is Edlich et al. 2011 on Bcl-xL/Bax.
Connections
[source]calcium-oscillation — corrects phantom “Chao 2011 Cell PMID 21458670” attribution[applies]STRC Calcium Oscillation Acoustic Therapy[see-also]1994-stemmer-klee-calcineurin-dual-calcium