ArticleJournal of molecular biology2019
Newly Discovered Micropeptide Regulators of SERCA Form Oligomers but Bind to the Pump as Monomers.
Article in Journal of molecular biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 74 citations in OpenAlex.
- A novel mitochondrial microprotein reprograms cellular bioenergetics and protects against hepatic steatosis.iScience · 2026Article
- Neprilysin mediated cleavage of phospholamban dysregulates SERCA in heart failure.bioRxiv : the preprint server for biology · 2026Article
- PIGBOS-CLCC1 interaction shapes cellular calcium dynamics and energy metabolism.Cell communication and signaling : CCS · 2026Article
- The Landscape of SERCA2 in Cardiovascular Diseases: Expression Regulation, Therapeutic Applications, and Emerging Roles.Biomolecules · 2026Review
- Microprotein, macro-effect: DWORF as a therapeutic strategy in heart failure.Frontiers in cell and developmental biology · 2026Review
- The SERCA-PLN-DWORF axis in cardiometabolic disease: mechanisms and therapeutic perspectives.Cardiovascular diabetology · 2025Review
- Stress-Induced calcium mishandling in cardiac (Patho)physiology.Cellular and molecular life sciences : CMLS · 2025Review
- Allosteric Modulation of SERCA Pumps in Health and Disease: Structural Dynamics, Posttranslational Modifications, and Therapeutic Potential.Journal of molecular biology · 2025Review
- The Quaternary Structure of the Sodium Pump Regulatory Complex Is Altered by Mutations of a Site Associated with Familial Hemiplegic Migraine.Molecular neurobiology · 2025Article
- Structural Elements of Dwarf Open Reading Frame Required for Activation of the Sarco-Endoplasmic Reticulum Calcium Pump.Biochemistry · 2025Article
- Paradoxical SERCA2a Dysregulation Contributes to Atrial Fibrillation in a Model of Diet-Induced Obesity.International journal of molecular sciences · 2025Article
- Identification of a molecular resistor that controls UCP1-independent CaCell metabolism · 2025Article
- Emerging roles for microproteins as critical regulators of endoplasmic reticulum function and cellular homeostasis.Seminars in cell & developmental biology · 2025Review
- Article
- Another-regulin regulates cardiomyocyte calcium handling via integration of neuroendocrine signaling with SERCA2a activity.Journal of molecular and cellular cardiology · 2024Article
- SARS-CoV-2 envelope protein alters calcium signaling via SERCA interactions.Scientific reports · 2024Article
- Phosphorylation of phospholamban promotes SERCA2a activation by dwarf open reading frame (DWORF).Cell calcium · 2024Article
- Perimenopause Decreases SERCA2a Activity in the Hearts of a Mouse Model of Ovarian Failure.Biomolecules · 2024Article
- Replacement of Lys27 by asparagine in the SERCA regulator myoregulin: A CaBiochimica et biophysica acta. Molecular cell research · 2024Review
- Microproteins-Discovery, structure, and function.Proteomics · 2023Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
The recently-discovered single-span transmembrane proteins endoregulin (ELN), dwarf open reading frame (DWORF), myoregulin (MLN), and another-regulin (ALN) are reported to bind to the SERCA calcium pump in a manner similar to that of known regulators of SERCA activity, phospholamban (PLB) and sarcolipin (SLN). To determine how micropeptide assembly into oligomers affects the availability of the micropeptide to bind to SERCA in a regulatory complex, we used co-immunoprecipitation and fluorescence resonance energy transfer (FRET) to quantify micropeptide oligomerization and SERCA-binding. Micropeptides formed avid homo-oligomers with high-order stoichiometry (n > 2 protomers per homo-oligomer), but it was the monomeric form of all micropeptides that interacted with SERCA. In view of these two alternative binding interactions, we evaluated the possibility that oligomerization occurs at the expense of SERCA-binding. However, even the most avidly oligomeric micropeptide species still showed robust FRET with SERCA, and there was a surprising positive correlation between oligomerization affinity and SERCA-binding. This comparison of micropeptide family members suggests that the same structural determinants that support oligomerization are also important for binding to SERCA. Moreover, the unique oligomerization/SERCA-binding profile of DWORF is in harmony with its distinct role as a PLB-competing SERCA activator, in contrast to the inhibitory function of the other SERCA-binding micropeptides.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.