Although intrinsically disordered proteins or protein domains (IDPs or IDD) are less abundant in bacteria than in eukaryotes, their presence in pathogenic bacterial proteins is important for protein-protein interactions. The protein tyrosine kinase A (PtkA) from Mycobacterium tuberculosis possesses an 80-residue disordered region (IDD ) of unknown function, located N-terminally to the well-folded kinase core domain. Here, we characterize the conformation of IDD under varying biophysical conditions and phosphorylation using NMR-spectroscopy. Our results confirm that the N-terminal domain of PtkA exists as an IDD at physiological pH. Furthermore, phosphorylation of IDD increases the activity of PtkA. Our findings will complement future approaches in understanding molecular mechanisms of key proteins in pathogenic virulence.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1002/1873-3468.13022 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Insights into conformational ensembles of compositionally identical disordered peptidomimetics.
Polym Chem
August 2024
Department of Chemistry, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
While the conformational ensembles of disordered peptides and peptidomimetics are complex and challenging to characterize, they are a critical component in the paradigm connecting macromolecule sequence, structure, and function. In molecules that do not adopt a single predominant conformation, the conformational ensemble contains rich structural information that, if accessible, can provide a fundamental understanding related to desirable functions such as cell penetration of a therapeutic or the generation of tunable enzyme-mimetic architecture. To address the fundamental challenge of describing broad conformational ensembles, we developed a model system of peptidomimetics comprised of polar glycine and hydrophobic -butylglycine to characterize using a suite of analytical techniques.
View Article and Find Full Text PDFInherent asymmetry of Rpd3S coordinates its nucleosome engagement and association with elongating RNA polymerase II.
Nat Struct Mol Biol
January 2025
Department of Biochemistry and Molecular Cell Biology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
The Rpd3S histone deacetylase complex has a crucial role in genomic integrity by deacetylating transcribed nucleosomes following RNA polymerase (Pol) II passage. Cryo-EM studies highlight the importance of asymmetrical Rco1-Eaf3 dimers in nucleosome binding, yet the interaction dynamics with nucleosomal substrates alongside elongating Pol II are poorly understood. Here we demonstrate the essential function of the Rco1 N-terminal intrinsically disordered region (IDR) in modulating Pol II association, in which K/R mutations within the Rco1 IDR impair interaction of Rpd3S with the C-terminal domain (CTD) of Rpb1, without affecting nucleosome recognition or complex integrity.
View Article and Find Full Text PDFThe sequence-structure-function relationship of intrinsic ERα disorder.
Nature
January 2025
Case Comprehensive Cancer Center and Department of Nutrition, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
The oestrogen receptor (ER or ERα), a nuclear hormone receptor that drives most breast cancer, is commonly activated by phosphorylation at serine 118 within its intrinsically disordered N-terminal transactivation domain. Although this modification enables oestrogen-independent ER function, its mechanism has remained unclear despite ongoing clinical trials of kinase inhibitors targeting this region. By integration of small-angle X-ray scattering and nuclear magnetic resonance spectroscopy with functional studies, we show that serine 118 phosphorylation triggers an unexpected expansion of the disordered domain and disrupts specific hydrophobic clustering between two aromatic-rich regions.
View Article and Find Full Text PDFSingle-molecule analysis reveals that IPMK enhances the DNA-binding activity of the transcription factor SRF.
Nucleic Acids Res
January 2025
Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro, Yuseong-gu, Daejeon 34141, Republic of Korea.
Serum response factor (SRF) is a master transcription factor that regulates immediate early genes and cytoskeletal remodeling genes. Despite its importance, the mechanisms through which SRF stably associates with its cognate promoter remain unknown. Our biochemical and protein-induced fluorescence enhancement analyses showed that the binding of SRF to serum response element was significantly increased by inositol polyphosphate multikinase (IPMK), an SRF cofactor.
View Article and Find Full Text PDFInfection-induced lysine lactylation enables herpesvirus immune evasion.
Sci Adv
January 2025
Department of Molecular Biology, Princeton University, Lewis Thomas Laboratory, Washington Road, Princeton, NJ 08544, USA.
Aerobic glycolysis is a hallmark of many viral infections, leading to substantial accumulation of lactate. However, the regulatory roles of lactate during viral infections remain poorly understood. Here, we report that human cytomegalovirus (HCMV) infection leverages lactate to induce widespread protein lactylation and promote viral spread.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!