ArticleProceedings of the National Academy of Sciences of the United States of America2009
Top-down high-resolution mass spectrometry of cardiac myosin binding protein C revealed that truncation alters protein phosphorylation state.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 110 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
110 citing papers in PubMed, 154 citations in OpenAlex.
- AMPK phosphorylation proceeds through hierarchical proteoform cascades revealed by integrated mass spectrometry.Science advances · 2026Article
- Mass spectrometry-based top-down proteomics for proteoform profiling of protein coronas.Nature protocols · 2026Review
- Parkinson's disease-specific α-Synuclein variants potentially drive Lewy body formation by engaging in promiscuous and non-functional interactions.Communications biology · 2026Article
- Proteomics of the heart.Physiological reviews · 2024Review
- Pilot Evaluation of the Long-Term Reproducibility of Capillary Zone Electrophoresis-Tandem Mass Spectrometry for Top-Down Proteomics of a Complex Proteome Sample.Journal of proteome research · 2024Article
- Computational approaches to identify sites of phosphorylation.Proteomics · 2024Review
- Top-down proteomics.Nature reviews. Methods primers · 2024Article
- Bringing into focus the central domains C3-C6 of myosin binding protein C.Frontiers in physiology · 2024Review
- Article
- Fourier-transform ion cyclotron resonance mass spectrometry for characterizing proteoforms.Mass spectrometry reviews · 2022Review
- Proteomic Analysis of the Functional Inward Rectifier Potassium Channel (Kir) 2.1 Reveals Several Novel Phosphorylation Sites.Biochemistry · 2021Article
- Novel Strategies to Address the Challenges in Top-Down Proteomics.Journal of the American Society for Mass Spectrometry · 2021Review
- Advances in Proteomics Allow Insights Into Neuronal Proteomes.Frontiers in molecular neuroscience · 2021Review
- Top-Down Proteomics of Endogenous Membrane Proteins Enabled by Cloud Point Enrichment and Multidimensional Liquid Chromatography-Mass Spectrometry.Analytical chemistry · 2020Article
- Distinct hypertrophic cardiomyopathy genotypes result in convergent sarcomeric proteoform profiles revealed by top-down proteomics.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Top-down proteomics: challenges, innovations, and applications in basic and clinical research.Expert review of proteomics · 2020Article
- Thorough Performance Evaluation of 213 nm Ultraviolet Photodissociation for Top-down Proteomics.Molecular & cellular proteomics : MCP · 2020Article
- Comprehensive Characterization of the Recombinant Catalytic Subunit of cAMP-Dependent Protein Kinase by Top-Down Mass Spectrometry.Journal of the American Society for Mass Spectrometry · 2019Article
- Human cardiac myosin-binding protein C restricts actin structural dynamics in a cooperative and phosphorylation-sensitive manner.The Journal of biological chemistry · 2019Article
- Middle-Down Multi-Attribute Analysis of Antibody-Drug Conjugates with Electron Transfer Dissociation.Analytical chemistry · 2019Article
50 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Cardiac myosin binding protein C (cMyBP-C), bound to the sarcomere's myosin thick filament, plays an important role in the regulation of muscle contraction. cMyBP-C is a large multidomain protein that interacts with myosin, titin, and possibly actin. Mutations in cMyBP-C are the most common known cause of heritable hypertrophic cardiomypathies. Phosphorylation of cMyBP-C plays an essential role in the normal cardiac function. cMyBP-C (142 kDa) has 81 serine and 73 threonine residues presenting a major challenge for unequivocal identification of specific phosphorylation sites. Top-down mass spectrometry, which directly analyzes intact proteins, is a powerful technique to universally observe and quantify protein posttranslational modifications without a priori knowledge. Here, we have extended top-down electron capture dissociation mass spectrometry to comprehensively characterize mouse cMyBP-C expressed in baculovirus. We have unambiguously identified all of the phosphorylation sites in the truncated (28-115 kDa) and full-length forms of cMyBP-C (142 kDa) and characterized the sequential phosphorylations, using a combination of top-down and middle-down (limited proteolysis) MS approach, which ensures full sequence coverage. Unit mass resolution and high mass accuracy (<5 ppm) have been achieved for a 115-kDa protein (the largest protein isotopically resolved to date). Remarkably, we discovered that truncations in recombinant proteins, even a seemingly minor one, can dramatically alter its phosphorylation state, which is significant because truncated recombinant proteins are routinely substituted for their full-length forms in crystal structure and functional studies. Our study provides direct evidence of alterations in the posttranslational state between the truncated and full-length recombinant proteins, which can lead to variations in structure and function.
Indexed as
Identifiers
What OpenQuestion holds
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.