Cellular and epigenetic perspective of protein stability and its implications in the biological system
Creators: name: Manav, Nisha
name: Jit, Bimal Prasad
name: Kataria, Babita
name: Sharma, Ashok
Publisher: name: Taylor & Francis
Year: 2024
Subjects: subject: Biophysics
subject: Biochemistry
subject: Genetics
subject: FOS: Biological sciences
subject: Molecular Biology
subject: Developmental Biology
subject: Cancer
subject: Inorganic Chemistry
subject: FOS: Chemical sciences
subject: Hematology
subject: Infectious Diseases
subject: FOS: Health sciences

description: Protein stability is a fundamental prerequisite in both experimental and therapeutic applications. Current advancements in high throughput experimental techniques and functional ontology approaches have elucidated that impairment in the structure and stability of proteins is intricately associated with the cause and cure of several diseases. Therefore, it is paramount to deeply understand the physical and molecular confounding factors governing the stability of proteins. In this review article, we comprehensively investigated the evolution of protein stability, examining its emergence over time, its relationship with organizational aspects and the experimental methods used to understand it. Furthermore, we have also emphasized the role of Epigenetics and its interplay with post-translational modifications (PTMs) in regulating the stability of proteins. Proteins are essential for life and are used in many medical treatments. Understanding what makes proteins stable can help us use them more effectively. This review looks at how different things like temperature and pH affect protein stability. It also discusses how chemical changes in cells, called epigenetic modifications, can impact protein stability. Understanding these factors can help us develop better treatments and therapies. Understanding protein stability is crucial in experiments and therapeutic implications. Our review explores how proteins evolve for stability, methods to study it and the influence of epigenetics and post-translational modifications. The composition of amino acids, their sequence, and their 3D folding pattern, played a key role in evolving the protein class in the cellular domain, conferring protein evolution. Intrinsically disordered proteins play a prominent role in regulating transcription, translation, cell cycle, and protein–protein interaction. Covalent modifications of the side chains, disulphide bond formation and proteolytic cleavage are paramount for protein stability. Epigenetics play a crucial role in gene expression and thus regulates protein function. DNA methylation, noncoding RNA and histone modification (includes methylation, acetylation/deacetylation, ubiquitination and phosphorylation) play pivotal roles in regulating protein stability. Lysine acetylation prevents the ubiquitylation of certain proteins by competing with the ubiquitin group at the same lysine site, enhancing the stability of target proteins. HDAC inhibitors like TSA or SAHA could potentially augment the stability of proteins in several diseases in clinical settings. Various PTMs on proteins induced by epigenetic players modulate the stability of proteins and determine their fate in different signaling conditions. N-terminal acetylation has been shown to play a pivotal role in controlling protein stability. Misfolded proteins are tagged with ubiquitin groups by ubiquitin ligases (E1, E2 and E3) and are marked for proteasomal degradation. The autophagy pathway attempts to degrade the proteins that are not degraded by the conventional proteasomal degradation pathway. In addition to epigenetics, understanding gene mutation and designing novel proteins by site-directed or random mutagenesis is highly important for precision medicine. A practical computational approach and logarithm must be implemented to predict a booming immunotherapeutic target.