8Y68

the crystal structure of apo CASK-CaMK

Summary for 8Y68

• Entry DOI: 10.2210/pdb8y68/pdb
• Descriptor: Peripheral plasma membrane protein CASK (2 entities in total)
• Functional Keywords: cask, camk domain, transport protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 76354.03

Authors

Li, W.,Feng, W. (deposition date: 2024-02-02, release date: 2025-08-06, Last modification date: 2025-11-19)

Primary citation

Li, W.,Wang, Y.,Feng, W.
Structural basis for the Ca 2+ /CaM-mediated regulation of CASK-CaMK.
Int.J.Biol.Macromol., 332:148495-148495, 2025

PubMed Abstract: As a member of the Ca/CaM-dependent protein kinase family, CASK contains an N-terminal CaMK domain that is regulated by Ca-bound CaM, while the underlying mechanism remains to be elucidated. Here, we determine the crystal structures of CASK-CaMK in different states: apo CASK-CaMK, CASK-CaMK in complex with CaM (the CaM-CASK complex) and CASK-CaMK in complex with CaM and Mint1 (the CaM-CASK-Mint1 complex). CASK-CaMK exhibits an inhibitory conformation with the αR2 helix of the autoregulatory domain (ARD) inserting into its nucleotide-binding pocket. Contrary to conventional CaM-mediated binding paradigms, in the CaM-CASK complex, only the C-terminal lobe of CaM (C-CaM) engages with the ARD of CASK-CaMK. This C-CaM binding induces the formation of an extended ARD α-helix that reshapes the nucleotide-binding pocket of CASK-CaMK to enhance its nucleotide-binding capacity. Correspondingly, in the CaM-CASK-Mint1 complex, similar C-CaM binding to CASK-CaMK leads to a slight opening of the CASK-Mint1 complex, and only the Mint1-CID (CASK-interaction domain) core is resolved association with CASK-CaMK. Taken together, CaM likely regulates CASK-CaMK through a C-CaM-dependent mechanism to tune its nucleotide-binding and target-recognition capacities.

PubMed: 41151710
DOI: 10.1016/j.ijbiomac.2025.148495

Experimental method

X-RAY DIFFRACTION (2.2 Å)