7E11

Crystal structure of PKAc-PLN R9C complex

Summary for 7E11

• Entry DOI: 10.2210/pdb7e11/pdb
• Descriptor: cAMP-dependent protein kinase catalytic subunit alpha, PLN, PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER, ... (4 entities in total)
• Functional Keywords: kinase, complex, transferase
• Biological source: Mus musculus (Mouse); More
• Total number of polymer chains: 2
• Total formula weight: 41406.43

Authors

Qin, J.,Lin, L.,Yuchi, Z. (deposition date: 2021-01-28, release date: 2022-04-27, Last modification date: 2024-11-20)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (3.43 Å)