7E0Z

Crystal structure of PKAc-PLN complex

7E0Z の概要

• エントリーDOI: 10.2210/pdb7e0z/pdb
• 分子名称: cAMP-dependent protein kinase catalytic subunit alpha, PLN, PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER, ... (5 entities in total)
• 機能のキーワード: kinase, complex, transferase
• 由来する生物種: Mus musculus (Mouse); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 43293.46

構造登録者

Qin, J.,Yuchi, Z. (登録日: 2021-01-28, 公開日: 2022-04-27, 最終更新日: 2024-10-23)

主引用文献

Qin, J.,Zhang, J.,Lin, L.,Haji-Ghassemi, O.,Lin, Z.,Woycechowsky, K.J.,Van Petegem, F.,Zhang, Y.,Yuchi, Z.
Structures of PKA-phospholamban complexes reveal a mechanism of familial dilated cardiomyopathy.
Elife, 11:-, 2022

PubMed Abstract: Several mutations identified in phospholamban (PLN) have been linked to familial dilated cardiomyopathy (DCM) and heart failure, yet the underlying molecular mechanism remains controversial. PLN interacts with sarco/endoplasmic reticulum Ca-ATPase (SERCA) and regulates calcium uptake, which is modulated by the protein kinase A (PKA)-dependent phosphorylation of PLN during the fight-or-flight response. Here, we present the crystal structures of the catalytic domain of mouse PKA in complex with wild-type and DCM-mutant PLNs. Our structures, combined with the results from other biophysical and biochemical assays, reveal a common disease mechanism: the mutations in PLN reduce its phosphorylation level by changing its conformation and weakening its interactions with PKA. In addition, we demonstrate that another more ubiquitous SERCA-regulatory peptide, called another-regulin (ALN), shares a similar mechanism mediated by PKA in regulating SERCA activity.

PubMed: 35297759
DOI: 10.7554/eLife.75346

実験手法

X-RAY DIFFRACTION (2.162 Å)