2OZA

Structure of p38alpha complex

2OZA の概要

• エントリーDOI: 10.2210/pdb2oza/pdb
• 分子名称: MAP kinase-activated protein kinase 2, Mitogen-activated protein kinase 14 (3 entities in total)
• 機能のキーワード: serine/threonine kinase, protein-protein complex, p38a, mk2, signaling protein-transferase complex, signaling protein/transferase
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Cytoplasm: P47811
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 83083.44

構造登録者

White, A.,Pargellis, C.A.,Studts, J.M.,Werneburg, B.G.,Farmer II, B.T. (登録日: 2007-02-25, 公開日: 2007-04-03, 最終更新日: 2024-02-21)

主引用文献

White, A.,Pargellis, C.A.,Studts, J.M.,Werneburg, B.G.,Farmer II, B.T.
Molecular basis of MAPK-activated protein kinase 2:p38 assembly
Proc.Natl.Acad.Sci.Usa, 104:6353-6358, 2007

PubMed Abstract: p38 MAPK and MAPK-activated protein kinase 2 (MK2) are key components of signaling pathways leading to many cellular responses, notably the proinflammatory cytokine production. The physical association of p38alpha isoform and MK2 is believed to be physiologically important for this signaling. We report the 2.7-A resolution crystal structure of the unphosphorylated complex between p38alpha and MK2. These protein kinases bind "head-to-head," present their respective active sites on approximately the same side of the heterodimer, and form extensive intermolecular interactions. Among these interactions, the MK2 Ile-366-Ala-390, which includes the bipartite nuclear localization signal, binds to the p38alpha-docking region. This binding supports the involvement of noncatalytic regions to the tight binding of the MK2:p38alpha binary assembly. The MK2 residues 345-365, containing the nuclear export signal, block access to the p38alpha active site. Some regulatory phosphorylation regions of both protein kinases engage in multiple interactions with one another in this complex. This structure gives new insights into the regulation of the protein kinases p38alpha and MK2, aids in the better understanding of their known cellular and biochemical studies, and provides a basis for understanding other regulatory protein-protein interactions involving signal transduction proteins.

PubMed: 17395714
DOI: 10.1073/pnas.0701679104

実験手法

X-RAY DIFFRACTION (2.7 Å)