10,059 results match your criteria n-terminal fragment

Upper Reference Limits for High-Sensitivity Cardiac Troponin T and N-Terminal Fragment of the Prohormone Brain Natriuretic Peptide in Patients With CKD.

Am J Kidney Dis 2021 Jul 19. Epub 2021 Jul 19.

University of Maryland School of Medicine, Department of Medicine.

Rationale & Objective: The utility of conventional upper reference limits (URL) for N-terminal pro brain natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hsTnT) in chronic kidney disease (CKD) remains debated. We analyzed the distribution of hsTnT and NT-proBNP in people with CKD in ambulatory settings to examine the diagnostic value of conventional URL in this population.

Study Design: Observational study. Read More

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Enzyme mediated incorporation of zirconium-89 or copper-64 into a fragment antibody for same day imaging of epidermal growth factor receptor.

Chem Sci 2021 Jul 25;12(26):9004-9016. Epub 2021 May 25.

School of Chemistry and Bio21 Molecular Science, Biotechnology Institute University of Melbourne Parkville Victoria 3010 Australia

Identification of tumors which over-express Epidermal Growth Factor Receptor (EGFR) is important in selecting patients for anti-EGFR therapies. Enzymatic bioconjugation was used to introduce positron-emitting radionuclides (Zr, Cu) into an anti-EGFR antibody fragment for Positron Emission Tomography (PET) imaging the same day as injection. A monovalent antibody fragment with high affinity for EGFR was engineered to include a sequence that is recognized by the transpeptidase sortase A. Read More

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A tale of two tails: Self-assembling properties of A- and B-chain parts of insulin's highly amyloidogenic H-fragment.

Int J Biol Macromol 2021 Jul 13;186:510-518. Epub 2021 Jul 13.

Faculty of Chemistry, Biological and Chemical Research Centre, University of Warsaw, 1 Pasteur Str., 02-093 Warsaw, Poland. Electronic address:

Due to the spontaneous transition of native insulin into therapeutically inactive amyloid, prolonged storage decreases effectiveness of the hormone in treatment of diabetes. Various regions of the amino acid sequence have been implicated in insulin aggregation. Here, we focus on smaller fragments of the highly amyloidogenic H-peptide comprising disulfide-bonded N-terminal sections of insulin's A-chain (13 residues) and B-chain (11 residues). Read More

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Crowding affects structural dynamics and contributes to membrane association of the NS3/4A complex.

Biophys J 2021 Jul 13. Epub 2021 Jul 13.

Centre of New Technologies, University of Warsaw, S. Banacha 2c, 02-097 Warsaw, Poland. Electronic address:

Using molecular dynamics simulations we describe how crowded environments affect the internal dynamics and diffusion of the hepatitis C virus proteases - NS3/4A. This protease plays a key role in viral replication and is successfully used as a target for anti-viral treatment. The NS3 enzyme requires a peptide cofactor, called NS4A, with its central part interacting with the NS3 β-sheet and flexible, protruding terminal tails that are unstructured in water solution. Read More

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The Role of Pyroptosis in Ischemic and Reperfusion Injury of the Heart.

J Cardiovasc Pharmacol Ther 2021 Jul 15:10742484211027405. Epub 2021 Jul 15.

Department of Physiology and Cell Biology, 12214University of South Alabama College of Medicine, Mobile, AL, USA.

While ischemia itself can kill heart muscle, much of the infarction after a transient period of coronary artery occlusion has been found to result from injury during reperfusion. Here we review the role of inflammation and possible pyroptosis in myocardial reperfusion injury. Current evidence suggests pyroptosis's contribution to infarction may be considerable. Read More

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Site-specific internal protein labeling through trans-splicing.

Int J Biol Macromol 2021 Jul 5;186:40-46. Epub 2021 Jul 5.

College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, PR China. Electronic address:

Atypical S1 and S11 split inteins have been used for N-terminal or C-terminal protein labeling. Here we reported a novel site-specific internal protein labeling method based on two atypical split inteins, Ter DnaE3 S11 and Rma DnaB S1. Protein-peptide trans-splicing activity was first demonstrated in vitro between a short peptide (Flag tag, FLAG) and two recombinant proteins (Maltose binding protein, MBP, and Thioredoxin, Trx) by trans-splicing between MBP-TE3S11N (MBP-N fragment of Ter DnaE3 S11), TE3S11C-FLAG-RBS1N (C fragment of Ter DnaE3 S11-FLAG-N fragment of Rma DnaB S1), and RBS1C-Trx (C fragment of Rma DnaB S1-Trx). Read More

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Neurotoxicity of oligomers of phosphorylated Tau protein carrying tauopathy-associated mutation is inhibited by prion protein.

Biochim Biophys Acta Mol Basis Dis 2021 Jul 8:166209. Epub 2021 Jul 8.

Nencki Institute of Experimental Biology of Polish Academy of Sciences, 3 Pasteur Str., 02-093 Warsaw, Poland. Electronic address:

Tauopathies, including Alzheimer's disease (AD), are manifested by the deposition of well-characterized amyloid aggregates of Tau protein in the brain. However, it is rather unlikely that these aggregates constitute the major form of Tau responsible for neurodegenerative changes. Currently, it is postulated that the intermediates termed as soluble oligomers, assembled on the amyloidogenic pathway, are the most neurotoxic form of Tau. Read More

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Serum resistin levels and resistin gene polymorphism in patients with acne vulgaris: does it correlate with disease severity?

Int J Dermatol 2021 Jul 7. Epub 2021 Jul 7.

Medical Biochemistry and Molecular Biology Department, Menoufia University, Shebin EL-Kom, Egypt.

Background: Acne vulgaris is a disease that inflames the sebaceous gland with multiple etiologies. Many proinflammatory adipokines contribute to this pathogenesis. Resistin is a proinflammatory mediator that activates kappa B, a nuclear factor, and c-Jun N-terminal kinases pathways inducing toll-like receptor-2, interleukin-1, 6, and tumor necrosis factor alpha. Read More

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Conserved residues in the extracellular loop 2 regulate Stachel-mediated activation of ADGRG2.

Sci Rep 2021 Jul 7;11(1):14060. Epub 2021 Jul 7.

Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA.

Cleavage and dissociation of a large N-terminal fragment and the consequent unmasking of a short sequence (Stachel) remaining on the N-terminus have been proposed as mechanisms of activation of some members of the adhesion G protein-coupled receptor (aGPCR) family. However, the identity of residues that play a role in the activation of aGPCRs by the cognate Stachel remains largely unknown. Protein sequence alignments revealed a conserved stretch of residues in the extracellular loop 2 (ECL2) of all 33 members of the aGPCR family. Read More

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Enhanced β2-microglobulin binding of a "navigator" molecule bearing a single-chain variable fragment antibody for artificial switching of metabolic processing pathways.

Biomater Sci 2021 Jul 6. Epub 2021 Jul 6.

Department of Biomedical Engineering, National Cerebral and Cardiovascular Center (NCVC) Research Institute, 6-1 Kishibe-Shimmachi, Suita, Osaka 564-8565, Japan.

Kidney dysfunction increases the blood levels of β2-microglobulin (β2-m), triggering dialysis-related amyloidosis. Previously, we developed a navigator molecule, consisting of a fusion protein of the N-terminal domain of apolipoprotein E (ApoE NTD) and the α3 domain of the major histocompatibility complex class I (MHC α3), for switching the metabolic processing pathway of β2-m from the kidneys to the liver. However, the β2-m binding of ApoE NTD-MHC α3 was impaired in the blood. Read More

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Bacillus amyloliquefaciens exopolysaccharide preparation induces glucagon-like peptide 1 secretion through the activation of bitter taste receptors.

Int J Biol Macromol 2021 Jun 30;185:562-571. Epub 2021 Jun 30.

Department of Biological Science and Technology, National Pingtung University of Science and Technology, No. 1, Shuehfu Rd., Neipu Township, Pingtung 912301, Taiwan. Electronic address:

The exopolysaccharide preparation of Bacillus amyloliquefaciens amy-1 (EPS) regulates glycemic levels and promotes glucagon-like peptide 1 (GLP-1) secretion in vivo and in vitro. This study aimed to identify the molecular mechanism underlying EPS-induced GLP-1 secretion. HEK293T cells stably expressing human Gα-gustducin were used as a heterologous system for expressing the genes of human bitter taste receptor (T2R) 10, 14, 30, 38 (PAV), 38 (AVI), 43, and 46, which were expressed as recombinant proteins with an N-terminal tag composed of a Lucy peptide and a human somatostatin receptor subtype 3 fragment for membrane targeting and a C-terminal red fluorescent protein for expression monitoring. Read More

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Latency, thermal stability, and identification of an inhibitory compound of mirolysin, a secretory protease of the human periodontopathogen .

J Enzyme Inhib Med Chem 2021 Dec;36(1):1267-1281

Department of Microbiology, Faculty of Biochemistry, Biophysics, and Biotechnology, Jagiellonian University, Krakow, Poland.

Mirolysin is a secretory protease of , a member of the dysbiotic oral microbiota responsible for periodontitis. In this study, we show that mirolysin latency is achieved by a "cysteine-switch" mechanism exerted by Cys23 in the N-terminal profragment. Mutation of Cys23 shortened the time needed for activation of the zymogen from several days to 5 min. Read More

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December 2021

Crystal structures of Val58Ile tryptophan repressor in a domain-swapped array in the presence and absence of L-tryptophan.

Acta Crystallogr F Struct Biol Commun 2021 Jul 30;77(Pt 7):215-225. Epub 2021 Jul 30.

Chemistry Department, Princeton University, Princeton, NJ 08544, USA.

The crystal structures of domain-swapped tryptophan repressor (TrpR) variant Val58Ile before and after soaking with the physiological ligand L-tryptophan (L-Trp) indicate that L-Trp occupies the same location in the domain-swapped form as in native dimeric TrpR and makes equivalent residue contacts. This result is unexpected because the ligand binding-site residues arise from three separate polypeptide chains in the domain-swapped form. This work represents the first published structure of a domain-swapped form of TrpR with L-Trp bound. Read More

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A new mouse mutant with cleavage-resistant versican and isoform-specific versican mutants demonstrate that proteolysis at the Glu-Ala peptide bond in the V1 isoform is essential for interdigital web regression.

Matrix Biol Plus 2021 Jun 14;10:100064. Epub 2021 May 14.

Department of Biomedical Engineering-ND20, Cleveland Clinic Lerner Research Institute, 9500 Euclid Avenue, Cleveland, OH 44195, United States.

Two inherent challenges in the mechanistic interpretation of protease-deficient phenotypes are defining the specific substrate cleavages whose reduction generates the phenotypes and determining whether the phenotypes result from loss of substrate function, substrate accumulation, or loss of a function(s) embodied in the substrate fragments. Hence, recapitulation of a protease-deficient phenotype by a cleavage-resistant substrate would stringently validate the importance of a proteolytic event and clarify the underlying mechanisms. Versican is a large proteoglycan required for development of the circulatory system and proper limb development, and is cleaved by ADAMTS proteases at the Glu-Ala peptide bond located in its alternatively spliced GAGβ domain. Read More

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Comparative host interactomes of the SARS-CoV-2 nonstructural protein 3 and human coronavirus homologs.

Mol Cell Proteomics 2021 Jun 26:100120. Epub 2021 Jun 26.

Department of Chemistry, Vanderbilt University, Nashville, TN, USA; Department of Biological Sciences, Vanderbilt University, Nashville, TN, USA; Vanderbilt Institute for Infection, Immunology, and Inflammation, Vanderbilt University Medical Center, Nashville, TN, USA. Electronic address:

Human coronaviruses have become an increasing threat to global health; three highly pathogenic strains have emerged since the early 2000s, including most recently SARS-CoV-2, the cause of COVID-19. A better understanding of the molecular mechanisms of coronavirus pathogenesis is needed, including how these highly virulent strains differ from those that cause milder, common-cold like disease. While significant progress has been made in understanding how SARS-CoV-2 proteins interact with the host cell, non-structural protein 3 (nsp3) has largely been omitted from the analyses. Read More

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Seneca Valley Virus 3C Protease Induces Pyroptosis by Directly Cleaving Porcine Gasdermin D.

J Immunol 2021 Jun 28. Epub 2021 Jun 28.

State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China; and Key Laboratory of Preventive Veterinary Medicine in Hubei Province, The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, China

Seneca Valley virus (SVV), a newly emerging virus belonging to the family, has caused vesicular disease in the swine industry. However, the molecular mechanism of viral pathogenesis remains poorly understood. This study revealed that SVV infection could induce pyroptosis in SK6 cells in a caspase-dependent and -independent manner. Read More

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Expression of Human ACE2 N-terminal Domain, Part of the Receptor for SARS-CoV-2, in Fusion With Maltose-Binding Protein, Ribonuclease I and Human RNase A.

Front Microbiol 2021 11;12:660149. Epub 2021 Jun 11.

New England Biolabs, Inc., Ipswich, MA, United States.

The SARS-CoV-2 viral genome contains a positive-strand single-stranded RNA of ∼30 kb. Human ACE2 protein is the receptor for SARS-CoV-2 virus attachment and infection. We propose to use ribonucleases (RNases) as antiviral agents to destroy the viral genome . Read More

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A Crystallographic Snapshot of SARS-CoV-2 Main Protease Maturation Process.

J Mol Biol 2021 Jun 24;433(18):167118. Epub 2021 Jun 24.

Institute of Physics of Sao Carlos, University of Sao Paulo, Av. Joao Dagnone, 1100, Jardim Santa Angelina, Sao Carlos 13563-120, Brazil. Electronic address:

SARS-CoV-2 is the causative agent of COVID-19. The dimeric form of the viral M is responsible for the cleavage of the viral polyprotein in 11 sites, including its own N and C-terminus. The lack of structural information for intermediary forms of M is a setback for the understanding its self-maturation process. Read More

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A New Chemoenzymatic Semisynthetic Approach Provides Insight into the Role of Phosphorylation beyond Exon1 of Huntingtin and Reveals N-Terminal Fragment Length-Dependent Distinct Mechanisms of Aggregation.

J Am Chem Soc 2021 Jul 23;143(26):9798-9812. Epub 2021 Jun 23.

Laboratory of Molecular and Chemical Biology of Neurodegeneration, School of Life Sciences, Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland.

Huntington's disease is a neurodegenerative disorder caused by the expansion of a polyglutamine repeat (>36Q) in the N-terminal domain of the huntingtin protein (Htt), which renders the protein or fragments thereof more prone to aggregate and form inclusions. Although several Htt N-terminal fragments of different lengths have been identified within Htt inclusions, most studies on the mechanisms, sequence, and structural determinants of Htt aggregation have focused on the Httexon1 (Httex1). Herein, we investigated the aggregation properties of mutant N-terminal Htt fragments of various lengths (Htt171, Htt140, and Htt104) in comparison to mutant Httex1 (mHttex1). Read More

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Gasdermin-E-mediated pyroptosis participates in the pathogenesis of Crohn's disease by promoting intestinal inflammation.

Cell Rep 2021 Jun;35(11):109265

Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. Electronic address:

Crohn's disease (CD) is a kind of refractory intestinal inflammatory diseases. Pyroptosis was recently identified as a gasdermin-mediated proinflammatory cell death. However, it is unclear whether gasdermin-mediated pyroptosis participates in the pathogenesis of CD. Read More

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The N-terminal domain of the prion protein is required and sufficient for liquid-liquid phase separation: A crucial role of the Aβ-binding domain.

J Biol Chem 2021 Jun 6;297(1):100860. Epub 2021 Jun 6.

Department of Biochemistry of Neurodegenerative Diseases, Institute of Biochemistry and Pathobiochemistry, Ruhr University Bochum, Bochum, Germany; Cluster of Excellence RESOLV, Ruhr University Bochum, Bochum, Germany. Electronic address:

Formation of biomolecular condensates through liquid-liquid phase separation (LLPS) has been described for several pathogenic proteins linked to neurodegenerative diseases and is discussed as an early step in the formation of protein aggregates with neurotoxic properties. In prion diseases, neurodegeneration and formation of infectious prions is caused by aberrant folding of the cellular prion protein (PrP). PrP is characterized by a large intrinsically disordered N-terminal domain and a structured C-terminal globular domain. Read More

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Identification of Antibacterial Immunity Proteins in Escherichia coli using MALDI-TOF-TOF-MS/MS and Top-Down Proteomic Analysis.

J Vis Exp 2021 May 23(171). Epub 2021 May 23.

Produce Safety & Microbiology, Western Regional Research Center, Agricultural Research Service, U.S. Department of Agriculture.

This protocol identifies the immunity proteins of the bactericidal enzymes: colicin E3 and bacteriocin, produced by a pathogenic Escherichia coli strain using antibiotic induction, and identified by MALDI-TOF-TOF tandem mass spectrometry and top-down proteomic analysis with software developed in-house. The immunity protein of colicin E3 (Im3) and the immunity protein of bacteriocin (Im-Bac) were identified from prominent b- and/or y-type fragment ions generated by the polypeptide backbone cleavage (PBC) on the C-terminal side of aspartic acid, glutamic acid, and asparagine residues by the aspartic acid effect fragmentation mechanism. The software rapidly scans in silico protein sequences derived from the whole genome sequencing of the bacterial strain. Read More

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A novel bioengineered fragment peptide of Vasostatin-1 exerts smooth muscle pharmacological activities and anti-angiogenic effects via blocking VEGFR signalling pathway.

Comput Struct Biotechnol J 2021 3;19:2664-2675. Epub 2021 May 3.

Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Avenida de Universidade, Taipa, Macau SAR, China.

Chromogranin A (CgA) is a hydrophilic glycoprotein released by post-ganglionic sympathetic neurons. CgA consists of a single peptide chain containing numerous paired basic residues, which are typical cleavage sites in prohormones to generate bioactive peptides. It is recognized as a diagnostic and prognostic serum marker for neuroendocrine tumours. Read More

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Protonectin peptides target lipids, act at the interface and selectively kill metastatic breast cancer cells while preserving morphological integrity.

J Colloid Interface Sci 2021 May 25;601:517-530. Epub 2021 May 25.

Departamento de Física, Universidade Estadual Paulista (UNESP), Instituto de Biociências Letras e Ciências Exatas (IBILCE), R. Cristóvão Colombo, 2265, 15054-000 São José do Rio Preto, SP, Brazil; Departamento de Química e Ciências Ambientais, Universidade Estadual Paulista (UNESP), Instituto de Biociências Letras e Ciências Exatas (IBILCE), R. Cristóvão Colombo, 2265, 15054-000 São José do Rio Preto, SP, Brazil. Electronic address:

Despite the need for innovative compounds as antimicrobial and anticancer agents, natural sources of peptides remain underexplored. Protonectin (PTN), a cationic dodecapeptide of pharmacological interest, presents large hydrophobicity that is associated with the tendency to aggregate and supposedly influences bioactivity. A disaggregating role was assigned to PTN' N-terminal fragment (PTN), which enhances the bioactivity of PTN in a 1:1 mixture (PTN/PTN). Read More

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Characterization of Adeno-Associated Virus Capsid Proteins with Two Types of VP3-Related Components by Capillary Gel Electrophoresis and Mass Spectrometry.

Hum Gene Ther 2021 Jul 16. Epub 2021 Jul 16.

Department of Biotechnology, Graduate School of Engineering, Osaka University, Suita, Japan.

Recombinant adeno-associated virus is a leading platform in human gene therapy. The adeno-associated virus (AAV) capsid is composed of three viral proteins (VPs): VP1, VP2, and VP3. To ensure the safety of AAV-based gene therapy products, the stoichiometry of VPs of AAV vector should be carefully monitored. Read More

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A Systematic Evaluation of Semispecific Peptide Search Parameter Enables Identification of Previously Undescribed N-Terminal Peptides and Conserved Proteolytic Processing in Cancer Cell Lines.

Proteomes 2021 May 25;9(2). Epub 2021 May 25.

Institute for Surgical Pathology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany.

Liquid chromatography-tandem mass spectrometry (LC-MS/MS) has become the most commonly used technique in explorative proteomic research. A variety of open-source tools for peptide-spectrum matching have become available. Most analyses of explorative MS data are performed using conventional settings, such as fully specific enzymatic constraints. Read More

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Highly Conserved -Terminal Region of Indian Hedgehog -Fragment Contributes to Its Auto-Processing and Multimer Formation.

Biomolecules 2021 May 25;11(6). Epub 2021 May 25.

Bio-X-Renji Hospital Research Center, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200240, China.

Hedgehog (HH) is a highly conserved secretory signalling protein family mainly involved in embryonic development, homeostasis, and tumorigenesis. HH is generally synthesised as a precursor, which subsequently undergoes autoproteolytic cleavage to generate an amino-terminal fragment (HH-N), mediating signalling, and a carboxyl-terminal fragment (HH-C), catalysing the auto-processing reaction. The -terminal region of HH-N is required for HH multimer formation to promote signal transduction, whilst the functions of the -terminal region of HH-N remain ambiguous. Read More

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Rotavirus as an Expression Platform of Domains of the SARS-CoV-2 Spike Protein.

Vaccines (Basel) 2021 May 3;9(5). Epub 2021 May 3.

Department of Biology, Indiana University, Bloomington, IN 47405, USA.

Among vaccines administered to children are those targeting rotavirus, a segmented double-stranded RNA virus that represents a major cause of severe gastroenteritis. To explore the feasibility of establishing a combined rotavirus-SARS-CoV-2 vaccine, we generated recombinant (r)SA11 rotaviruses with modified segment 7 RNAs that contained coding cassettes for NSP3, a translational 2A stop-restart signal, and a FLAG-tagged portion of the SARS-CoV-2 spike (S) protein: S1 fragment, N-terminal domain (NTD), receptor-binding domain (RBD), extended RBD (ExRBD), or S2 core (CR) domain. Generation of rSA11 containing the S1 coding sequence required a sequence insertion of 2. Read More

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β-Defensins from common goby (Pomatoschistus microps) and silver trevally (Pseudocaranx georgianus): Molecular characterization and phylogenetic analysis.

Mol Biol Rep 2021 May 1;48(5):4943-4951. Epub 2021 Jun 1.

Department of Marine Biology, Microbiology and Biochemistry, School of Marine Sciences, Cochin University of Science and Technology, Fine Arts Avenue, Kochi, Kerala, 682016, India.

Antimicrobial peptides (AMPs) are biologically active molecules involved in host defense present in a variety of organisms. They are an integral component of innate immunity, forming a front line of defense against potential pathogens, including antibiotic-resistant ones. Fishes are proven to be a prospective source of AMPs as they are constantly being challenged by a variety of pathogens and the AMPs are reported to play an inevitable role in fish immunity. Read More

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Cardiac myosin-binding protein C interaction with actin is inhibited by compounds identified in a high-throughput fluorescence lifetime screen.

J Biol Chem 2021 May 28;297(1):100840. Epub 2021 May 28.

Department of Cellular & Molecular Medicine, University of Arizona, Tucson Arizona, USA. Electronic address:

Cardiac myosin-binding protein C (cMyBP-C) interacts with actin and myosin to modulate cardiac muscle contractility. These interactions are disfavored by cMyBP-C phosphorylation. Heart failure patients often display decreased cMyBP-C phosphorylation, and phosphorylation in model systems has been shown to be cardioprotective against heart failure. Read More

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