6X5Q

Cocrystal structure of human CaMKII-alpha (CAMK2A)kinase domain and GluA1

6X5Q の概要

• エントリーDOI: 10.2210/pdb6x5q/pdb
• 関連するPDBエントリー: 6X5G
• 分子名称: Calcium/calmodulin-dependent protein kinase type II subunit alpha, Glutamate receptor 1, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: camkii, kinase, human, camk2a, transferase
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 33148.15

構造登録者

Ozden, C.,Stratton, M.M.,Garman, S.C. (登録日: 2020-05-26, 公開日: 2020-12-23, 最終更新日: 2023-10-18)

主引用文献

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

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: 35830796
DOI: 10.1016/j.celrep.2022.111064

実験手法

X-RAY DIFFRACTION (2.14 Å)