Summary for 7UJR
| Entry DOI | 10.2210/pdb7ujr/pdb |
| Related | 6x5g |
| Descriptor | Calcium/calmodulin-dependent protein kinase type II subunit alpha, Glutamate receptor ionotropic, NMDA 2B, 1,2-ETHANEDIOL, ... (5 entities in total) |
| Functional Keywords | camkii, kinase, human, camk2a, transferase |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 2 |
| Total formula weight | 33585.50 |
| Authors | Ozden, C.,Santos, N.J.,Stratton, M.M.,Garman, S.C. (deposition date: 2022-03-31, release date: 2022-04-13, Last modification date: 2023-10-18) |
| Primary citation | Ozden, C.,Sloutsky, R.,Mitsugi, T.,Santos, N.,Agnello, E.,Gaubitz, C.,Foster, J.,Lapinskas, E.,Esposito, E.A.,Saneyoshi, T.,Kelch, B.A.,Garman, S.C.,Hayashi, Y.,Stratton, M.M. CaMKII binds both substrates and activators at the active site. Cell Rep, 40:111064-111064, 2022 Cited by PubMed Abstract: Ca/calmodulin-dependent protein kinase II (CaMKII) is a signaling protein required for long-term memory. When activated by Ca/CaM, it sustains activity even after the Ca dissipates. In addition to the well-known autophosphorylation-mediated mechanism, interaction with specific binding partners also persistently activates CaMKII. A long-standing model invokes two distinct S and T sites. If an interactor binds at the T-site, then it will preclude autoinhibition and allow substrates to be phosphorylated at the S site. Here, we specifically test this model with X-ray crystallography, molecular dynamics simulations, and biochemistry. Our data are inconsistent with this model. Co-crystal structures of four different activators or substrates show that they all bind to a single continuous site across the kinase domain. We propose a mechanistic model where persistent CaMKII activity is facilitated by high-affinity binding partners that kinetically compete with autoinhibition by the regulatory segment to allow substrate phosphorylation. PubMed: 35830796DOI: 10.1016/j.celrep.2022.111064 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.95 Å) |
Structure validation
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