ArticleThe EMBO journal2000
The interaction of titin and alpha-actinin is controlled by a phospholipid-regulated intramolecular pseudoligand mechanism.
Article in The EMBO journal, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 120 citations in OpenAlex.
- In silico conformational dynamics of the α-actinin-2 actin-binding domain upon phosphorylation.Biophysical journal · 2026Article
- SimHS-AFMfit-MD: An Integrative Approach for Inferring Alpha-Actinin Atomic Conformational Dynamics.Nano letters · 2026Article
- Paralemmin-1 controls the nanoarchitecture of the neuronal submembrane cytoskeleton.Science advances · 2025Article
- Structural and functional insights into α-actinin isoforms and their implications in cardiovascular disease.The Journal of general physiology · 2025Review
- Protein-extending ACTN2 frameshift variants cause variable myopathy phenotypes by protein aggregation.Annals of clinical and translational neurology · 2024Article
- Article
- An optimized approach to study nanoscale sarcomere structure utilizing super-resolution microscopy with nanobodies.PloS one · 2024Article
- Signatures of Cysteine Oxidation on Muscle Structural and Contractile Proteins Are Associated with Physical Performance and Muscle Function in Older Adults: Study of Muscle, Mobility and Aging (SOMMA).medRxiv : the preprint server for health sciences · 2023Article
- Rupture of Splenic Artery Aneurysm in Patient with ACTN2 Mutation.Journal of clinical medicine · 2023Article
- Actin Bundles Dynamics and Architecture.Biomolecules · 2023Review
- Mutation update for the ACTN2 gene.Human mutation · 2022Review
- A novel frameshift ACTN2 variant causes a rare adult-onset distal myopathy with multi-minicores.CNS neuroscience & therapeutics · 2021Article
- The Importance of Alpha-Actinin Proteins in Platelet Formation and Function, and Their Causative Role in Congenital Macrothrombocytopenia.International journal of molecular sciences · 2021Review
- Novel insights into sarcomere regulatory systems control of cardiac thin filament activation.The Journal of general physiology · 2021Article
- Mechanosignaling pathways alter muscle structure and function by post-translational modification of existing sarcomeric proteins to optimize energy usage.Journal of muscle research and cell motility · 2021Article
- Molecular basis of F-actin regulation and sarcomere assembly via myotilin.PLoS biology · 2021Article
- Manipulation of Focal Adhesion Signaling by Pathogenic Microbes.International journal of molecular sciences · 2021Review
- Calcium modulates the domain flexibility and function of an α-actinin similar to the ancestral α-actinin.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Three-dimensional structure of the basketweave Z-band in midshipman fish sonic muscle.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Adhesions Assemble!-Autoinhibition as a Major Regulatory Mechanism of Integrin-Mediated Adhesion.Frontiers in molecular biosciences · 2019Review
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The assembly of stable cytoskeletal structures from dynamically recycled molecules requires developmental and spatial regulation of protein interactions. In muscle, titin acts as a molecular ruler organizing the actin cytoskeleton via interactions with many sarcomeric proteins, including the crosslinking protein alpha-actinin. An interaction between the C-terminal domain of alpha-actinin and titin Z-repeat motifs targets alpha-actinin to the Z-disk. Here we investigate the cellular regulation of this interaction. alpha-actinin is a rod shaped head-to-tail homodimer. In contrast to C-terminal fragments, full-length alpha-actinin does not bind Z-repeats. We identify a 30-residue Z-repeat homologous sequence between the actin-binding and rod regions of alpha-actinin that binds the C-terminal domain with nanomolar affinity. Thus, Z-repeat binding is prevented by this 'pseudoligand' interaction between the subunits of the alpha-actinin dimer. This autoinhibition is relieved upon binding of the Z-disk lipid phosphatidylinositol-bisphosphate to the actin-binding domain. We suggest that this novel mechanism is relevant to control the site-specific interactions of alpha-actinin during sarcomere assembly and turnover. The intramolecular contacts defined here also constrain a structural model for intrasterical regulation of all alpha-actinin isoforms.
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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.