Medicine and Health Sciences Commons^™

New Evidence Of The Importance Of Weak Interactions In The Formation Of Pml-Bodies, Alexander V. Fonin, Sergey A. Silonov, Anna S. Fefilova, Olesya V. Stepanenko, Anastasia A. Gavrilova, Alexey V. Petukhov, Anna E. Romanovich, Anna L. Modina, Tatiana S. Zueva, Evgeniy M. Nedelyaev, Nadejda M. Pleskach, Irina M. Kuznetsova, Vladimir N. Uversky, Konstantin K. Turoverov, Mirya L. Kuranova

Molecular Medicine Faculty Publications

In this work, we performed a comparative study of the formation of PML bodies by full-length PML isoforms and their C-terminal domains in the presence and absence of endogenous PML. Based on the analysis of the distribution of intrinsic disorder predisposition in the amino acid sequences of PML isoforms, regions starting from the amino acid residue 395 (i.e., sequences encoded by exons 4–6) were assigned as the C-terminal domains of these proteins. We demonstrate that each of the full-sized nuclear isoforms of PML is capable of forming nuclear liquid-droplet compartments in the absence of other PML isoforms. These droplets possess …

Limosilactobacillus Fermentum Strain 3872: Antibacterial And Immunoregulatory Properties And Synergy With Prebiotics Against Socially Significant Antibiotic-Resistant Infections Of Animals And Humans, Vyacheslav M. Abramov, Igor V. Kosarev, Andrey V. Machulin, Tatiana V. Priputnevich, Irina O. Chikileva, Eugenia I. Deryusheva, Tatiana N. Abashina, Almira D. Donetskova, Alexander N. Panin, Vyacheslav G. Melnikov, Natalia E. Suzina, Ilya N. Nikonov, Marina V. Selina, Valentin S. Khlebnikov, Vadim K. Sakulin, Raisa N. Vasilenko, Vladimir A. Samoilenko, Vladimir N. Uversky, Andrey V. Karlyshev

Molecular Medicine Faculty Publications

Limosilactobacillus fermentum strain 3872 (LF3872) was originally isolated from the breast milk of a healthy woman during lactation and the breastfeeding of a child. The high-quality genome sequencing of LF3872 was performed, and a gene encoding a unique bacteriocin was discovered. It was established that the bacteriocin produced by LF3872 (BLF3872) belongs to the family of cell-wall-degrading proteins that cause cell lysis. The antibacterial properties of LF3872 were studied using test cultures of antibiotic-resistant Gram-positive and Gram-negative pathogens. Gram-positive pathogens (Staphylococcus aureus strain 8325-4 and S. aureus strain IIE CI-SA 1246) were highly sensitive to the bacteriolytic action of LF3872. …

Bioactive Peptides: Synthesis, Sources, Applications, And Proposed Mechanisms Of Action, Mohsen Akbarian, Ali Khani, Sara Eghbalpour, Vladimir N. Uversky

Molecular Medicine Faculty Publications

Bioactive peptides are a group of biological molecules that are normally buried in the structure of parent proteins and become active after the cleavage of the proteins. Another group of peptides is actively produced and found in many microorganisms and the body of organisms. Today, many groups of bioactive peptides have been marketed chemically or recombinantly. This article reviews the various production methods and sources of these important/ubiquitous and useful biomolecules. Their applications, such as antimicrobial, antihypertensive, antioxidant activities, blood-lipid-lowering effect, opioid role, antiobesity, ability to bind minerals, antidiabetic, and antiaging effects, will be explored. The types of pathways proposed …

Arrangement Of Hydrogen Bonds In Aqueous Solutions Of Different Globular Proteins, Amber R. Titus, Pedro P. Madeira, Luisa A. Ferreira, Alexander I. Belgovskiy, Elizabeth K. Mann, Jay Adin Mann Jr., William V. Meyer, Anthony E. Smart, Vladimir N. Uversky, Boris Zaslavsky

Molecular Medicine Faculty Publications

This work presents the first evidence that dissolved globular proteins change the arrangement of hydrogen bonds in water, with different proteins showing quantitatively different effects. Using ATR-FTIR (attenuated total reflection—Fourier transform infrared) spectroscopic analysis of OH-stretch bands, we obtain quantitative estimates of the relative amounts of the previously reported four subpopulations of water structures coexisting in a variety of aqueous solutions. Where solvatochromic dyes can measure the properties of solutions of non-ionic polymers, the results correlate well with ATR-FTIR measurements. In protein solutions to which solvatochromic dye probes cannot be applied, NMR (nuclear magnetic resonance) spectroscopy was used for the …

Are The Functions Of Milk Exosomes Restricted To Their Protein Cargoes?, Elrashdy M. Redwan, Vladimir N. Uversky

Molecular Medicine Faculty Publications

No abstract provided.

Bayesian Molecular Dating Analyses Combined With Mutational Profiling Suggest An Independent Origin And Evolution Of Sars-Cov-2 Omicron Ba.1 And Ba.2 Sub-Lineages, Naveen Kumar, Rahul Kaushik, Ashutosh Singh, Vladimir N. Uversky, Kam Y. J. Zhang, Upasana Sahu, Sandeep Bhatia, Aniket Sanyal

Molecular Medicine Faculty Publications

The ongoing evolution of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has resulted in the recent emergence of a highly divergent variant of concern (VOC) defined as Omicron or B.1.1.529. This VOC is of particular concern because it has the potential to evade most therapeutic antibodies and has undergone a sustained genetic evolution, resulting in the emergence of five distinct sub-lineages. However, the evolutionary dynamics of the initially identified Omicron BA.1 and BA.2 sub-lineages remain poorly understood. Herein, we combined Bayesian phylogenetic analysis, mutational profiling, and selection pressure analysis to track the virus’s genetic changes that drive the early evolutionary dynamics of …

Interferon-Β Activity Is Affected By S100b Protein, Alexey S. Kazakov, Alexander D. Sofin, Nadezhda V. Avkhacheva, Eugenia I. Deryusheva, Victoria A. Rastrygina, Maria E. Permyakova, Vladimir N. Uversky, Eugene A. Permyakov, Sergei E. Permyakov

Molecular Medicine Faculty Publications

Interferon-β (IFN-β) is a pleiotropic cytokine secreted in response to various pathological conditions and is clinically used for therapy of multiple sclerosis. Its application for treatment of cancer, infections and pulmonary diseases is limited by incomplete understanding of regulatory mechanisms of its functioning. Recently, we reported that IFN-β activity is affected by interactions with S100A1, S100A4, S100A6, and S100P proteins, which are members of the S100 protein family of multifunctional Ca2+-binding proteins possessing cytokine-like activities (Int J Mol Sci. 2020;21(24):9473). Here we show that IFN-β interacts with one more representative of the S100 protein family, the S100B protein, involved in …

Nanoparticles For Coronavirus Control, Maryam Kianpour, Mohsen Akbarian, Vladimir N. Uversky

Molecular Medicine Faculty Publications

More than 2 years have passed since the SARS-CoV-2 outbreak began, and many challenges that existed at the beginning of this pandemic have been solved. Some countries have been able to overcome this global challenge by relying on vaccines against the virus, and vaccination has begun in many countries. Many of the proposed vaccines have nanoparticles as carriers, and there are different nano-based diagnostic approaches for rapid detection of the virus. In this review article, we briefly examine the biology of SARS-CoV-2, including the structure of the virus and what makes it pathogenic, as well as describe biotechnological methods of …

Hepatitis C Virus Infection And Intrinsic Disorder In The Signaling Pathways Induced By Toll-Like Receptors, Elrashdy M. Redwan, Abdullah A. Aljadawi, Vladimir N. Uversky

Molecular Medicine Faculty Publications

In this study, we examined the interplay between protein intrinsic disorder, hepatitis C virus (HCV) infection, and signaling pathways induced by Toll-like receptors (TLRs). To this end, 10 HCV proteins, 10 human TLRs, and 41 proteins from the TLR-induced downstream pathways were considered from the prevalence of intrinsic disorder. Mapping of the intrinsic disorder to the HCV-TLR interactome and to the TLR-based pathways of human innate immune response to the HCV infection demonstrates that substantial levels of intrinsic disorder are characteristic for proteins involved in the regulation and execution of these innate immunity pathways and in HCV-TLR interaction. Disordered regions, …

Insights Into The Structural Properties Of Sars-Cov-2 Main Protease, Ibrahim Y. Akbaryak, Sule I. Caglayan, Lukasz Kurgan, Vladimir N. Uversky, Orkid Coskuner-Weber

Molecular Medicine Faculty Publications

SARS-CoV-2 is the infectious agent responsible for the coronavirus disease since 2019, which is the viral pneumonia pandemic worldwide. The structural knowledge on SARS-CoV-2 is rather limited. These limitations are also applicable to one of the most attractive drug targets of SARS-CoV-2 proteins – namely, main protease Mpro, also known as 3C-like protease (3CLpro). This protein is crucial for the processing of the viral polyproteins and plays crucial roles in interfering viral replication and transcription. In fact, although the crystal structure of this protein with an inhibitor was solved, Mpro conformational dynamics in aqueous solution is usually studied by molecular …

The Aqueous Humor Proteome Is Intrinsically Disordered, Mak B. Djulbegovic, Vladimir N. Uversky

Molecular Medicine Faculty Publications

No abstract provided.

Specific S100 Proteins Bind Tumor Necrosis Factor And Inhibit Its Activity, Alexey S. Kazakov, Marina Y. Zemskova, Gleb K. Rystsov, Alisa A. Vologzhannikova, Eugenia I. Deryusheva, Victoria A. Rastrygina, Andrey S. Sokolov, Maria E. Permyakova, Ekaterina A. Litus, Vladimir N. Uversky, Eugene A. Permyakov, Sergei E. Permyakov

Molecular Medicine Faculty Publications

Tumor necrosis factor (TNF) inhibitors (anti-TNFs) represent a cornerstone of the treatment of various immune-mediated inflammatory diseases and are among the most commercially successful therapeutic agents. Knowledge of TNF binding partners is critical for identification of the factors able to affect clinical efficacy of the anti-TNFs. Here, we report that among eighteen representatives of the multifunctional S100 protein family, only S100A11, S100A12 and S100A13 interact with the soluble form of TNF (sTNF) in vitro. The lowest equilibrium dissociation constants (Kd) for the complexes with monomeric sTNF determined using surface plasmon resonance spectroscopy range from 2 nM to 28 nM. The …

Mechanism Of Phase Separation In Aqueous Two-Phase Systems, Amber R. Titus, Pedro P. Madeira, Luisa A. Ferreira, Vladimir Y. Chernyak, Vladimir N. Uversky, Boris Y. Zaslavsky

Molecular Medicine Faculty Publications

Liquid-liquid phase separation underlies the formation of membrane-less organelles inside living cells. The mechanism of this process can be examined using simple aqueous mixtures of two or more solutes, which are able to phase separate at specific concentration thresholds. This work presents the first experimental evidence that mesoscopic changes precede visually detected macroscopic phase separation in aqueous mixtures of two polymers and a single polymer and salt. Dynamic light scattering (DLS) analysis indicates the formation of mesoscopic polymer agglomerates in these systems. These agglomerates increase in size with increasing polymer concentrations prior to visual phase separation. Such mesoscopic changes are …

Fight Fire With Fire: The Need For A Vaccine Based On Intrinsic Disorder And Structural Flexibility, Vladimir N. Uversky

Molecular Medicine Faculty Publications

The absence of advancement in finding efficient vaccines for several human viruses, such as hepatitis C virus (HCV), human immunodeficiency virus type 1 (HIV-1), and herpes simplex viruses (HSVs) despite 30, 40, and even 60 years of research, respectively, is unnerving. Among objective reasons for such failure are the highly glycosylated nature of proteins used as primary vaccine targets against these viruses and the presence of neotopes and cryptotopes, as well as high mutation rates of the RNA viruses HCV and HIV-1 and the capability to establish latency by HSVs. However, the lack of success in utilization of the structure-based …

Intrinsic Disorder As A Natural Preservative: High Levels Of Intrinsic Disorder In Proteins Found In The 2600-Year-Old Human Brain, Aaron S. Mohammed, Vladimir N. Uversky

Molecular Medicine Faculty Publications

Proteomic analysis revealed the preservation of many proteins in the Heslington brain (which is at least 2600-year-old brain tissue uncovered within the skull excavated in 2008 from a pit in Heslington, Yorkshire, England). Five of these proteins—“main proteins”: heavy, medium, and light neurofilament proteins (NFH, NFM, and NFL), glial fibrillary acidic protein (GFAP), and myelin basic (MBP) protein—are engaged in the formation of non-amyloid protein aggregates, such as intermediate filaments and myelin sheath. We used a wide spectrum of bioinformatics tools to evaluate the prevalence of functional disorder in several related sets of proteins, such as the main proteins and …

Bioinformatics-Based Characterization Of The Sequence Variability Of Zika Virus Polyprotein And Envelope Protein (E), Carlos Polanco, Vladimir N. Uversky, Alberto Huberman, Gilberto Vargas-Alarcón, Jorge Alberto Castañón González, Thomas Buhse, Enrique Hernández Lemus, Martha Rios Castro, Erika Jeannette López Oliva, Sergio Enrique Solís Nájera

Molecular Medicine Faculty Publications

Background: Zika virus, which is widely spread and infects humans through the bites of Aedes albopictus and Aedes aegypti female mosquitoes, represents a serious global health issue.

Objective: The objective of the present study is to computationally characterize Zika virus polyproteins (UniProt Name: PRO_0000443018 [residues 1-3423], PRO_0000445659 [residues 1-3423] and PRO_0000435828 [residues 1-3419]) and their envelope proteins using their physico-chemical properties.

Methods: To achieve this, the Polarity Index Method (PIM) profile and the Protein Intrinsic Disorder Predisposition (PIDP) profile of 3 main groups of proteins were evaluated: structural proteins extracted from specific Databases, Zika virus polyproteins, and their envelope proteins …

Erythropoietin Interacts With Specific S100 Proteins, Alexey S. Kazakov, Eugenia I. Deryusheva, Andrey S. Sokolov, Maria E. Permyakova, Ekaterina A. Litus, Victoria A. Rastrygina, Vladimir N. Uversky, Eugene A. Permyakov, Sergei E. Permyakov

Molecular Medicine Faculty Publications

Erythropoietin (EPO) is a clinically significant four-helical cytokine, exhibiting erythropoietic, cytoprotective, immunomodulatory, and cancer-promoting activities. Despite vast knowledge on its signaling pathways and physiological effects, extracellular factors regulating EPO activity remain underexplored. Here we show by surface plasmon resonance spectroscopy, that among eighteen members of Ca2+-binding proteins of the S100 protein family studied, only S100A2, S100A6 and S100P proteins specifically recognize EPO with equilibrium dissociation constants ranging from 81 nM to 0.5 µM. The interactions occur exclusively under calcium excess. Bioinformatics analysis showed that the EPO-S100 interactions could be relevant to progression of neoplastic diseases, including cancer, and other diseases. …

Msh3 Homology And Potential Recombination Link To Sars-Cov-2 Furin Cleavage Site, Balamurali K. Ambati, Akhil Varshney, Kenneth Lundstrom, Giorgio Palù, Bruce D. Uhal, Vladimir N. Uversky, Adam M. Brufsky

Molecular Medicine Faculty Publications

Among numerous point mutation differences between the SARS-CoV-2 and the bat RaTG13 coronavirus, only the 12-nucleotide furin cleavage site (FCS) exceeds 3 nucleotides. A BLAST search revealed that a 19 nucleotide portion of the SARS-CoV-2 genome encompassing the furin cleavage site is a 100% complementary match to a codon-optimized proprietary sequence that is the reverse complement of the human mutS homolog (MSH3). The reverse complement sequence present in SARS-CoV-2 may occur randomly but other possibilities must be considered. Recombination in an intermediate host is an unlikely explanation. Single stranded RNA viruses such as SARS-CoV-2 utilize negative strand RNA templates in …

Editorial: Intrinsically Disordered Proteins And Regions: The Challenge To The Structure-Function Relationship, Angelo Toto, Pietro Sormanni, Cristina Paissoni, Vladimir N. Uversky

Molecular Medicine Faculty Publications

No abstract provided.

Early Taurine Administration As A Means For Halting The Cytokine Storm Progression In Covid-19 Patients, Alberto Rubio-Casillas, Ramesh C. Gupta, Elrashdy M. Redwan, Vladimir N. Uversky, Raied A. Badierah

Molecular Medicine Faculty Publications

Around the world, more than 6.2 million individuals have died as a result of coronavirus disease 2019 (COVID-19). According to a recent survey conducted among immunologists, epidemiologists, and virologists, this disease is expected to become endemic. This implies that the disease could have a continuous presence and/or normal frequency in the population. Pharmacological interventions to prevent infection, as well as to treat the patients at an early phase of illness to avoid hospitalization are essential additions to the vaccines. Taurine is known to inhibit the generation of all inflammatory mediators linked to the cytokine storm. It can also protect against …

Looking At The Pathogenesis Of The Rabies Lyssavirus Strain Pasteur Vaccins Through A Prism Of The Disorder-Based Bioinformatics, Surya Dhulipala, Vladimir N. Uversky

Molecular Medicine Faculty Publications

Rabies is a neurological disease that causes between 40,000 and 70,000 deaths every year. Once a rabies patient has become symptomatic, there is no effective treatment for the illness, and in unvaccinated individuals, the case-fatality rate of rabies is close to 100%. French scientists Louis Pasteur and Émile Roux developed the first vaccine for rabies in 1885. If administered before the virus reaches the brain, the modern rabies vaccine imparts long-lasting immunity to the virus and saves more than 250,000 people every year. However, the rabies virus can suppress the host’s immune response once it has entered the cells of …

Theater In The Self-Cleaning Cell: Intrinsically Disordered Proteins Or Protein Regions Acting With Membranes In Autophagy, Hana Popelka, Vladimir N. Uversky

Molecular Medicine Faculty Publications

Intrinsically disordered proteins and protein regions (IDPs/IDPRs) are mainly involved in signaling pathways, where fast regulation, temporal interactions, promiscuous interactions, and assemblies of structurally diverse components including membranes are essential. The autophagy pathway builds, de novo, a membrane organelle, the autophagosome, using carefully orchestrated interactions between proteins and lipid bilayers. Here, we discuss molecular mechanisms related to the protein disorder-based interactions of the autophagy machinery with membranes. We describe not only membrane binding phenomenon, but also examples of membrane remodeling processes including membrane tethering, bending, curvature sensing, and/or fragmentation of membrane organelles such as the endoplasmic reticulum, which is an …

Intrinsic Disorder In Bap1 And Its Association With Uveal Melanoma, Mak B. Djulbegovic, David J. Taylor, Vladimir N. Uversky, Anat Galor, Carol L. Shields, Carol L. Karp

Molecular Medicine Faculty Publications

Background: Specific subvariants of uveal melanoma (UM) are associated with increased rates of metastasis compared to other subvariants. BRCA1 (BReast CAncer gene 1)-associated protein-1 (BAP1) is encoded by a gene that has been linked to aggressive behavior in UM. Methods: We evaluated BAP1 for the presence of intrinsically disordered protein regions (IDPRs) and its protein–protein interactions (PPI). We evaluated specific sequence-based features of the BAP1 protein using a set of bioinformatic databases, predictors, and algorithms. Results: We show that BAP1’s structure contains extensive IDPRs as it is highly enriched in proline residues (the most disordered amino acid; p-value < 0.05), the average percent of predicted disordered residues (PPDR) was 57.34%, and contains 9 disorder-based binding sites (ie. molecular recognition features (MoRFs)). BAP1’s intrinsic disorder allows it to engage in a complex PPI network with at least 49 partners (p-value < 1.0 × 10−16). Conclusion: These findings show that BAP1 contains IDPRs and an intricate PPI network. Mutations in UM that are associated with the BAP1 gene may alter the function of the IDPRs embedded into its structure. These findings develop the understanding of UM and may provide a target for potential novel therapies to treat this aggressive neoplasm.

Calcium-Bound S100p Protein Is A Promiscuous Binding Partner Of The Four-Helical Cytokines, Alexey S. Kazakov, Eugenia I. Deryusheva, Maria E. Permyakova, Andrey S. Sokolov, Victoria A. Rastrygina, Vladimir N. Uversky, Eugene A. Permyakov, Sergei E. Permyakov

Molecular Medicine Faculty Publications

S100 proteins are multifunctional calcium-binding proteins of vertebrates that act intracellularly, extracellularly, or both, and are engaged in the progression of many socially significant diseases. Their extracellular action is typically mediated by the recognition of specific receptor proteins. Recent studies indicate the ability of some S100 proteins to affect cytokine signaling through direct interaction with cytokines. S100P was shown to be the S100 protein most actively involved in interactions with some four-helical cytokines. To assess the selectivity of the S100P protein binding to four-helical cytokines, we have probed the interaction of Ca2+-bound recombinant human S100P with a panel of 32 …

Sars-Cov-2: A Master Of Immune Evasion, Alberto Rubio-Casillas, Elrashdy M. Redwan, Vladimir N. Uversky

Molecular Medicine Faculty Publications

Viruses and their hosts have coevolved for a long time. This coevolution places both the pathogen and the human immune system under selective pressure; on the one hand, the immune system has evolved to combat viruses and virally infected cells, while viruses have developed sophisticated mechanisms to escape recognition and destruction by the immune system. SARS-CoV-2, the pathogen that is causing the current COVID-19 pandemic, has shown a remarkable ability to escape antibody neutralization, putting vaccine efficacy at risk. One of the virus’s immune evasion strategies is mitochondrial sabotage: by causing reactive oxygen species (ROS) production, mitochondrial physiology is impaired, …

Ferritinophagy And Α-Synuclein: Pharmacological Targeting Of Autophagy To Restore Iron Regulation In Parkinson’S Disease, Matthew K. Boag, Angus Roberts, Vladimir N. Uversky, Linlin Ma, Des R. Richardson, Dean L. Pountney

Molecular Medicine Faculty Publications

A major hallmark of Parkinson’s disease (PD) is the fatal destruction of dopaminergic neurons within the substantia nigra pars compacta. This event is preceded by the formation of Lewy bodies, which are cytoplasmic inclusions composed of α-synuclein protein aggregates. A triad contribution of α-synuclein aggregation, iron accumulation, and mitochondrial dysfunction plague nigral neurons, yet the events underlying iron accumulation are poorly understood. Elevated intracellular iron concentrations up-regulate ferritin expression, an iron storage protein that provides cytoprotection against redox stress. The lysosomal degradation pathway, autophagy, can release iron from ferritin stores to facilitate its trafficking in a process termed ferritinophagy. Aggregated …

Would New Sars-Cov-2 Variants Change The War Against Covid-19?, Elrashdy M. Redwan, Fatma Elrashdy, Alaa A.A. Aljabali, Wagner Baetas-Da-Cruz, Debmalya Barh, Adam M. Brufsky, Sk. Sarif Hassan, Kenneth Lundstrom, Ángel Serrano-Aroca, Kazuo Takayama, Murtaza M. Tambuwala, Bruce D. Uhal, Vladimir N. Uversky

Molecular Medicine Faculty Publications

The scientific, private, and industrial sectors use a wide variety of technological platforms available to achieve protection against SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), including vaccines. However, the virus evolves continually into new highly virulent variants, which might overcome the protection provided by vaccines and may re-expose the population to infections. Mass vaccinations should be continued in combination with more or less mandatory non-pharmaceutical interventions. Therefore, the key questions to be answered are: (i) How to identify the primary and secondary infections of SARS-CoV-2? (ii) Why are neutralizing antibodies not long-lasting in both cases of natural infections and post-vaccinations? …

A Study On The Nature Of Sars-Cov-2 Using The Shell Disorder Models: Reproducibility, Evolution, Spread, And Attenuation, Gerard Kian-Meng Goh, A. Keith Dunker, James A. Foster, Vladimir N. Uversky

Molecular Medicine Faculty Publications

The basic tenets of the shell disorder model (SDM) as applied to COVID-19 are that the harder outer shell of the virus shell (lower PID—percentage of intrinsic disorder—of the membrane protein M, PIDM) and higher flexibility of the inner shell (higher PID of the nucleocapsid protein N, PIDN) are correlated with the contagiousness and virulence, respectively. M protects the virion from the anti-microbial enzymes in the saliva and mucus. N disorder is associated with the rapid replication of the virus. SDM predictions are supported by two experimental observations. The first observation demonstrated lesser and greater presence of the Omicron particles …

The Finite Size Effects And Two-State Paradigm Of Protein Folding, Artem Badasyan, Matjaz Valant, Jože Grdadolnik, Vladimir N. Uversky

Molecular Medicine Faculty Publications

The coil to globule transition of the polypeptide chain is the physical phenomenon behind the folding of globular proteins. Globular proteins with a single domain usually consist of about 30 to 100 amino acid residues, and this finite size extends the transition interval of the coil-globule phase transition. Based on the pedantic derivation of the two-state model, we introduce the number of amino acid residues of a polypeptide chain as a parameter in the expressions for two cooperativity measures and reveal their physical significance. We conclude that the 𝑘2 measure, defined as the ratio of van ’t Hoff and calorimetric …

On The Roles Of Intrinsically Disordered Proteins And Regions In Cell Communication And Signaling, Sarah E. Bondos, A. Keith Dunker, Vladimir N. Uversky

Molecular Medicine Faculty Publications

For proteins, the sequence → structure → function paradigm applies primarily to enzymes, transmembrane proteins, and signaling domains. This paradigm is not universal, but rather, in addition to structured proteins, intrinsically disordered proteins and regions (IDPs and IDRs) also carry out crucial biological functions. For these proteins, the sequence → IDP/IDR ensemble → function paradigm applies primarily to signaling and regulatory proteins and regions. Often, in order to carry out function, IDPs or IDRs cooperatively interact, either intra- or inter-molecularly, with structured proteins or other IDPs or intermolecularly with nucleic acids. In this IDP/IDR thematic collection published in Cell Communication …