ArticleFrontiers in physiology2020
Single-Molecule Force Spectroscopy on the N2A Element of Titin: Effects of Phosphorylation and CARP.
Article in Frontiers in physiology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 24 citations in OpenAlex.
- The titin N2A-MARP signalosome constrains muscle longitudinal hypertrophy in response to stretch.eLife · 2026Article
- Force-Induced Ankle Opening Reveals Mechanical Stabilization of the Ankle of Human β-Cardiac Myosin.ACS nano · 2026Article
- Mending the Achilles heels of titin in cardiac and musculoskeletal disease.Biophysical reviews · 2026Review
- Consecutive SSCs increase the SSC effect in skinned rat muscle fibres.Pflugers Archiv : European journal of physiology · 2025Article
- Modulation of Titin and Contraction-Regulating Proteins in a Rat Model of Heart Failure with Preserved Ejection Fraction: Limb vs. Diaphragmatic Muscle.International journal of molecular sciences · 2024Article
- Titin: roles in cardiac function and diseases.Frontiers in physiology · 2024Review
- Eccentric muscle contractions: from single muscle fibre to whole muscle mechanics.Pflugers Archiv : European journal of physiology · 2023Review
- Interdomain Linker Effect on the Mechanical Stability of Ig Domains in Titin.International journal of molecular sciences · 2022Article
- Atomic Force Microscopy (AFM) Applications in Arrhythmogenic Cardiomyopathy.International journal of molecular sciences · 2022Review
- Understanding the molecular basis of cardiomyopathy.American journal of physiology. Heart and circulatory physiology · 2022Review
- Titin kinase ubiquitination aligns autophagy receptors with mechanical signals in the sarcomere.EMBO reports · 2021Article
- Protein Unfolding: Denaturant vs. Force.Biomedicines · 2021Article
- The titin N2B and N2A regions: biomechanical and metabolic signaling hubs in cross-striated muscles.Biophysical reviews · 2021Review
- Protein nanomechanics in biological context.Biophysical reviews · 2021Review
- The Sarcomeric Spring Protein Titin: Biophysical Properties, Molecular Mechanisms, and Genetic Mutations Associated with Heart Failure and Cardiomyopathy.Current cardiology reports · 2021Review
- Titin N2A Domain and Its Interactions at the Sarcomere.International journal of molecular sciences · 2021Review
- The N2A region of titin has a unique structural configuration.The Journal of general physiology · 2021Article
- Muscle ankyrin repeat protein 1 (MARP1) locks titin to the sarcomeric thin filament and is a passive force regulator.The Journal of general physiology · 2021Article
- Molecular Characterisation of Titin N2A and Its Binding of CARP Reveals a Titin/Actin Cross-linking Mechanism.Journal of molecular biology · 2021Article
- Single-particle virology.Biophysical reviews · 2020Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 3 countries.
Funding
Abstract
Titin is a large filamentous protein that forms a sarcomeric myofilament with a molecular spring region that develops force in stretched sarcomeres. The molecular spring has a complex make-up that includes the N2A element. This element largely consists of a 104-residue unique sequence (N2A-Us) flanked by immunoglobulin domains (I80 and I81). The N2A element is of interest because it assembles a signalosome with CARP (Cardiac Ankyrin Repeat Protein) as an important component; CARP both interacts with the N2A-Us and I81 and is highly upregulated in response to mechanical stress. The mechanical properties of the N2A element were studied using single-molecule force spectroscopy, including how these properties are affected by CARP and phosphorylation. Three protein constructs were made that consisted of 0, 1, or 2 N2A-Us elements with flanking I80 and I81 domains and with specific handles at their ends for study by atomic force microscopy (AFM). The N2A-Us behaved as an entropic spring with a persistence length (Lp) of ∼0.35 nm and contour length (Lc) of ∼39 nm. CARP increased the Lp of the N2A-Us and the unfolding force of the Ig domains; force clamp experiments showed that CARP reduced the Ig domain unfolding kinetics. These findings suggest that CARP might function as a molecular chaperone that protects I81 from unfolding when mechanical stress is high. The N2A-Us was found to be a PKA substrate, and phosphorylation was blocked by CARP. Mass spectrometry revealed a PKA phosphosite (Ser-9895 in NP_001254479.2) located at the border between the N2A-Us and I81. AFM studies showed that phosphorylation affected neither the Lp of the N2A-Us nor the Ig domain unfolding force (F
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