7E0Z
Crystal structure of PKAc-PLN complex
Summary for 7E0Z
Entry DOI | 10.2210/pdb7e0z/pdb |
Descriptor | cAMP-dependent protein kinase catalytic subunit alpha, PLN, PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER, ... (5 entities in total) |
Functional Keywords | kinase, complex, transferase |
Biological source | Mus musculus (Mouse) More |
Total number of polymer chains | 2 |
Total formula weight | 43293.46 |
Authors | |
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 Cited by 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: 35297759DOI: 10.7554/eLife.75346 PDB entries with the same primary citation |
Experimental method | X-RAY DIFFRACTION (2.162 Å) |
Structure validation
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