3J4R

Pseudo-atomic model of the AKAP18-PKA Complex in a linear conformation derived from electron microscopy

3J4R の概要

• エントリーDOI: 10.2210/pdb3j4r/pdb
• 関連するPDBエントリー: 3J4Q
• EMDBエントリー: 5755 5756
• 分子名称: A-kinase anchor protein 18, cAMP-dependent protein kinase type II-alpha regulatory subunit, cAMP-dependent protein kinase catalytic subunit alpha (3 entities in total)
• 機能のキーワード: a-kinase anchoring protein, camp-dependent kinase, rii, pka regulatory subunit ii, phosphorylation, anchoring, intrinsic disorder, transferase
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 212024.42

構造登録者

Reichow, S.L.,Gonen, T. (登録日: 2013-09-25, 公開日: 2013-11-13, 最終更新日: 2024-02-21)

主引用文献

Smith, F.D.,Reichow, S.L.,Esseltine, J.L.,Shi, D.,Langeberg, L.K.,Scott, J.D.,Gonen, T.
Intrinsic disorder within an AKAP-protein kinase A complex guides local substrate phosphorylation.
Elife, 2:e01319-e01319, 2013

PubMed Abstract: Anchoring proteins sequester kinases with their substrates to locally disseminate intracellular signals and avert indiscriminate transmission of these responses throughout the cell. Mechanistic understanding of this process is hampered by limited structural information on these macromolecular complexes. A-kinase anchoring proteins (AKAPs) spatially constrain phosphorylation by cAMP-dependent protein kinases (PKA). Electron microscopy and three-dimensional reconstructions of type-II PKA-AKAP18γ complexes reveal hetero-pentameric assemblies that adopt a range of flexible tripartite configurations. Intrinsically disordered regions within each PKA regulatory subunit impart the molecular plasticity that affords an ∼16 nanometer radius of motion to the associated catalytic subunits. Manipulating flexibility within the PKA holoenzyme augmented basal and cAMP responsive phosphorylation of AKAP-associated substrates. Cell-based analyses suggest that the catalytic subunit remains within type-II PKA-AKAP18γ complexes upon cAMP elevation. We propose that the dynamic movement of kinase sub-structures, in concert with the static AKAP-regulatory subunit interface, generates a solid-state signaling microenvironment for substrate phosphorylation. DOI: http://dx.doi.org/10.7554/eLife.01319.001.

PubMed: 24192038
DOI: 10.7554/eLife.01319

実験手法

ELECTRON MICROSCOPY (35 Å)