Post-translational modifications of intrinsically disordered regions (IDRs) enable changes in sequence chemistry, which in turn can tune conformational behavior and molecular interactions. In this issue of The EMBO Journal, Gruijs da Silva et al disentangle the effect of hyperphosphorylation on the C-terminal domain of TDP-43, a key IDR implicated in Amyotrophic Lateral Sclerosis (ALS).
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http://dx.doi.org/10.15252/embj.2022111062 | DOI Listing |
Replication protein A (RPA) is a heterotrimeric single-strand DNA binding protein that is integral to DNA metabolism. Segregation of RPA functions in response to DNA damage is fine-tuned by hyperphosphorylation of the RPA32 subunit that is dependent on Cyclin-dependent kinase (Cdk)-mediated priming phosphorylation at the Ser-23 and Ser-29 sites. However, the mechanism of priming-driven hyperphosphorylation of RPA remains unresolved.
View Article and Find Full Text PDFNeurochem Int
October 2023
Institute of Pharmacology, Shandong First Medical University and Shandong Academy of Medical Sciences, Taian, 271021, China. Electronic address:
Nat Commun
March 2024
Frontiers Science Center for Transformative Molecules, School of Chemistry and Chemical Engineering, School of Biomedical Engineering, National Center for Translational Medicine, State Key Laboratory of Oncogenes and Related Genes, Shanghai Jiao Tong University, Shanghai, 200240, China.
NPJ Parkinsons Dis
September 2022
Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA.
α-Synuclein (αSyn) aggregation in Lewy bodies and neurites defines both familial and 'sporadic' Parkinson's disease. We previously identified α-helically folded αSyn tetramers, in addition to the long-known unfolded monomers, in normal cells. PD-causing αSyn mutations decrease the tetramer:monomer (T:M) ratio, associated with αSyn hyperphosphorylation and cytotoxicity in neurons and a motor syndrome of tremor and gait deficits in transgenic mice that responds in part to L-DOPA.
View Article and Find Full Text PDFEMBO J
April 2022
Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO, USA.
Post-translational modifications of intrinsically disordered regions (IDRs) enable changes in sequence chemistry, which in turn can tune conformational behavior and molecular interactions. In this issue of The EMBO Journal, Gruijs da Silva et al disentangle the effect of hyperphosphorylation on the C-terminal domain of TDP-43, a key IDR implicated in Amyotrophic Lateral Sclerosis (ALS).
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!