Sirtuin 3 overexpression preserves maximal sarco(endo)plasmic reticulum calcium ATPase activity in the skeletal muscle of mice subjected to high fat - high sucrose feeding.

Sarco(endo)plasmic reticulum calcium (Ca) ATPase (SERCA) transports Ca in muscle. Impaired SERCA activity may contribute to diabetic myopathy. Sirtuin (SIRT) 3 regulates muscle metabolism and function; however, it is unknown if SIRT3 regulates muscle SERCA activity or acetylation.

Accurate Sequence-Based Prediction of Deleterious nsSNPs with Multiple Sequence Profiles and Putative Binding Residues.

Non-synonymous single nucleotide polymorphisms (nsSNPs) may result in pathogenic changes that are associated with human diseases. Accurate prediction of these deleterious nsSNPs is in high demand. The existing predictors of deleterious nsSNPs secure modest levels of predictive performance, leaving room for improvements.

Intrinsic Disorder in Human RNA-Binding Proteins.

Although RNA-binding proteins (RBPs) are known to be enriched in intrinsic disorder, no previous analysis focused on RBPs interacting with specific RNA types. We fill this gap with a comprehensive analysis of the putative disorder in RBPs binding to six common RNA types: messenger RNA (mRNA), transfer RNA (tRNA), small nuclear RNA (snRNA), non-coding RNA (ncRNA), ribosomal RNA (rRNA), and internal ribosome RNA (irRNA). We also analyze the amount of putative intrinsic disorder in the RNA-binding domains (RBDs) and non-RNA-binding-domain regions (non-RBD regions).

Muscle-specific sirtuin 3 overexpression does not attenuate the pathological effects of high-fat/high-sucrose feeding but does enhance cardiac SERCA2a activity.

Obesity, type 2 diabetes, and heart disease are linked to an unhealthy diet. Sarco(endo)plasmic reticulum calcium (Ca ) ATPase 2a (SERCA2a) controls cardiac function by transporting Ca in cardiomyocytes. SERCA2a is altered by diet and acetylation, independently; however, it is unknown if diet alters cardiac SERCA2a acetylation.

DescribePROT: database of amino acid-level protein structure and function predictions.

We present DescribePROT, the database of predicted amino acid-level descriptors of structure and function of proteins. DescribePROT delivers a comprehensive collection of 13 complementary descriptors predicted using 10 popular and accurate algorithms for 83 complete proteomes that cover key model organisms. The current version includes 7.

Identification of Intrinsic Disorder in Complexes from the Protein Data Bank.

Background: Intrinsically disordered proteins or regions (IDPs or IDRs) lack stable structures in solution, yet often fold upon binding with partners. IDPs or IDRs are highly abundant in all proteomes and represent a significant modification of sequence → structure → function paradigm. The Protein Data Bank (PDB) includes complexes containing disordered segments bound to globular proteins, but the molecular mechanisms of such binding interactions remain largely unknown.

Understanding COVID-19 via comparative analysis of dark proteomes of SARS-CoV-2, human SARS and bat SARS-like coronaviruses.

The recently emerged coronavirus designated as SARS-CoV-2 (also known as 2019 novel coronavirus (2019-nCoV) or Wuhan coronavirus) is a causative agent of coronavirus disease 2019 (COVID-19), which is rapidly spreading throughout the world now. More than 1.21 million cases of SARS-CoV-2 infection and more than 67,000 COVID-19-associated mortalities have been reported worldwide till the writing of this article, and these numbers are increasing every passing hour.

Computational Prediction of Intrinsic Disorder in Protein Sequences with the disCoP Meta-predictor.

Intrinsically disordered proteins are either entirely disordered or contain disordered regions in their native state. These proteins and regions function without the prerequisite of a stable structure and were found to be abundant across all kingdoms of life. Experimental annotation of disorder lags behind the rapidly growing number of sequenced proteins, motivating the development of computational methods that predict disorder in protein sequences.

Prediction of Intrinsic Disorder with Quality Assessment Using QUARTER.

Intrinsically disordered regions (IDRs) are estimated to be highly abundant in nature. While only several thousand proteins are annotated with experimentally derived IDRs, computational methods can be used to predict IDRs for the millions of currently uncharacterized protein chains. Several dozen disorder predictors were developed over the last few decades.

Myokines as biomarkers of frailty and cardiovascular disease risk in females.

Frailty is a risk factor for cardiovascular disease (CVD). Biomarkers have the potential to detect the early stages of frailty, such as pre-frailty. Myokines may act as biomarkers of frailty-related disease progression, as a decline in muscle health is a hallmark of the frailty phenotype.

Disordered RNA-Binding Region Prediction with DisoRDPbind.

RNA chaperone activity is one of the many functions of intrinsically disordered regions (IDRs). IDRs function without the prerequisite of a stable structure. Instead, their functions arise from structural ensembles.

Mechanisms for the transition from physiological to pathological cardiac hypertrophy.

The heart is capable of responding to stressful situations by increasing muscle mass, which is broadly defined as cardiac hypertrophy. This phenomenon minimizes ventricular wall stress for the heart undergoing a greater than normal workload. At initial stages, cardiac hypertrophy is associated with normal or enhanced cardiac function and is considered to be adaptive or physiological; however, at later stages, if the stimulus is not removed, it is associated with contractile dysfunction and is termed as pathological cardiac hypertrophy.

Disordered Function Conjunction: On the in-silico function annotation of intrinsically disordered regions.

Intrinsically disorder regions (IDRs) lack a stable structure, yet perform biological functions. The functions of IDRs include mediating interactions with other molecules, including proteins, DNA, or RNA and entropic functions, including domain linkers. Computational predictors provide residue-level indications of function for disordered proteins, which contrasts with the need to functionally annotate the thousands of experimentally and computationally discovered IDRs.

Many-to-one binding by intrinsically disordered protein regions.

Disordered binding regions (DBRs), which are embedded within intrinsically disordered proteins or regions (IDPs or IDRs), enable IDPs or IDRs to mediate multiple protein-protein interactions. DBR-protein complexes were collected from the Protein Data Bank for which two or more DBRs having different amino acid sequences bind to the same (100% sequence identical) globular protein partner, a type of interaction herein called many-to-one binding. Two distinct binding profiles were identified: independent and overlapping.

DISOselect: Disorder predictor selection at the protein level.

The intense interest in the intrinsically disordered proteins in the life science community, together with the remarkable advancements in predictive technologies, have given rise to the development of a large number of computational predictors of intrinsic disorder from protein sequence. While the growing number of predictors is a positive trend, we have observed a considerable difference in predictive quality among predictors for individual proteins. Furthermore, variable predictor performance is often inconsistent between predictors for different proteins, and the predictor that shows the best predictive performance depends on the unique properties of each protein sequence.

Accuracy of protein-level disorder predictions.

Experimental annotations of intrinsic disorder are available for 0.1% of 147 000 000 of currently sequenced proteins. Over 60 sequence-based disorder predictors were developed to help bridge this gap.

Prehabilitation: The Right Medicine for Older Frail Adults Anticipating Transcatheter Aortic Valve Replacement, Coronary Artery Bypass Graft, and Other Cardiovascular Care.

The wait before elective cardiac intervention or surgery presents an opportunity to prevent further physiologic decline preoperatively in older patients. Implementation of prehabilitation programs decreases length of hospital stay postoperatively, decreases time spent in the intensive care unit, decreases postoperative complications, and improves self-reported quality of life postsurgery. Prehabilitation programs should adopt multimodal approaches including nutrition, exercise, and worry reduction to improve patient resilience in the preoperative period.

Intrinsically disordered domains: Sequence ➔ disorder ➔ function relationships.

Disordered domains are long regions of intrinsic disorder that ideally have conserved sequences, conserved disorder, and conserved functions. These domains were first noticed in protein-protein interactions that are distinct from the interactions between two structured domains and the interactions between structured domains and linear motifs or molecular recognition features (MoRFs). So far, disordered domains have not been systematically characterized.

Codon selection reduces GC content bias in nucleic acids encoding for intrinsically disordered proteins.

Protein-coding nucleic acids exhibit composition and codon biases between sequences coding for intrinsically disordered regions (IDRs) and those coding for structured regions. IDRs are regions of proteins that are folding self-insufficient and which function without the prerequisite of folded structure. Several authors have investigated composition bias or codon selection in regions encoding for IDRs, primarily in Eukaryota, and concluded that elevated GC content is the result of the biased amino acid composition of IDRs.

Computational Prediction of Secondary and Supersecondary Structures from Protein Sequences.

Many new methods for the sequence-based prediction of the secondary and supersecondary structures have been developed over the last several years. These and older sequence-based predictors are widely applied for the characterization and prediction of protein structure and function. These efforts have produced countless accurate predictors, many of which rely on state-of-the-art machine learning models and evolutionary information generated from multiple sequence alignments.

Quality assessment for the putative intrinsic disorder in proteins.

Motivation: While putative intrinsic disorder is widely used, none of the predictors provides quality assessment (QA) scores. QA scores estimate the likelihood that predictions are correct at a residue level and have been applied in other bioinformatics areas. We recently reported that QA scores derived from putative disorder propensities perform relatively poorly for native disordered residues.

Predicting Functions of Disordered Proteins with MoRFpred.

Intrinsically disordered proteins and regions are involved in a wide range of cellular functions, and they often facilitate protein-protein interactions. Molecular recognition features (MoRFs) are segments of intrinsically disordered regions that bind to partner proteins, where binding is concomitant with a transition to a structured conformation. MoRFs facilitate translation, transport, signaling, and regulatory processes and are found across all domains of life.

Intrinsically Disordered Proteome of Human Membrane-Less Organelles.

It is recognized now that various proteinaceous membrane-less organelles (PMLOs) are commonly found in cytoplasm, nucleus, and mitochondria of various eukaryotic cells (as well as in the chloroplasts of plant cells). Being different from the "traditional" membrane-encapsulated organelles, such as chloroplasts, endoplasmic reticulum, Golgi apparatus, lysosomes, mitochondria, nucleus, and vacuoles, PMLOs solve the cellular need to facilitate and regulate molecular interactions via reversible and controllable isolation of target molecules in specialized compartments. PMLOs possess liquid-like behavior and are believed to be formed as a result of biological liquid-liquid phase transitions (LLPTs, also known as liquid-liquid phase separation), where an intricate interplay between RNA and intrinsically disordered proteins (IDPs) or hybrid proteins containing ordered domains and intrinsically disordered protein regions (IDPRs) may play an important role.

Evidence for a Strong Correlation Between Transcription Factor Protein Disorder and Organismic Complexity.

Studies of diverse phylogenetic lineages reveal that protein disorder increases in concert with organismic complexity but that differences nevertheless exist among lineages. To gain insight into this phenomenology, we analyzed all of the transcription factor (TF) families for which sequences are known for 17 species spanning bacteria, yeast, algae, land plants, and animals and for which the number of different cell types has been reported in the primary literature. Although the fraction of disordered residues in TF sequences is often moderately or poorly correlated with organismic complexity as gauged by cell-type number (r2 < 0.