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Full-Text Articles in Medicine and Health Sciences
Networks Of Networks: An Essay On Multi-Level Biological Organization, Vladimir N. Uversky, Alessandro Giuliani
Networks Of Networks: An Essay On Multi-Level Biological Organization, Vladimir N. Uversky, Alessandro Giuliani
Molecular Medicine Faculty Publications
The multi-level organization of nature is self-evident: proteins do interact among them to give rise to an organized metabolism, while in the same time each protein (a single node of such interaction network) is itself a network of interacting amino-acid residues allowing coordinated motion of the macromolecule and systemic effect as allosteric behavior. Similar pictures can be drawn for structure and function of cells, organs, tissues, and ecological systems. The majority of biologists are used to think that causally relevant events originate from the lower level (the molecular one) in the form of perturbations, that “climb up” the hierarchy reaching …
On The Prevalence And Potential Functionality Of An Intrinsic Disorder In The Mers-Cov Proteome, Manal A. Alshehri, Manee M. Manee, Fahad H. Alqahtani, Badr M. Al-Shomrani, Vladimir N. Uversky
On The Prevalence And Potential Functionality Of An Intrinsic Disorder In The Mers-Cov Proteome, Manal A. Alshehri, Manee M. Manee, Fahad H. Alqahtani, Badr M. Al-Shomrani, Vladimir N. Uversky
Molecular Medicine Faculty Publications
Middle East respiratory syndrome is a severe respiratory illness caused by an infectious coronavirus. This virus is associated with a high mortality rate, but there is as of yet no effective vaccine or antibody available for human immunity/treatment. Drug design relies on understanding the 3D structures of viral proteins; however, arriving at such understanding is difficult for intrinsically disordered proteins, whose disorder-dependent functions are key to the virus’s biology. Disorder is suggested to provide viral proteins with highly flexible structures and diverse functions that are utilized when invading host organisms and adjusting to new habitats. To date, the functional roles …
On The Need To Develop Guidelines For Characterizing And Reporting Intrinsic Disorder In Proteins, Michael Vincent, Vladimir N. Uversky, Santiago Schnell
On The Need To Develop Guidelines For Characterizing And Reporting Intrinsic Disorder In Proteins, Michael Vincent, Vladimir N. Uversky, Santiago Schnell
Molecular Medicine Faculty Publications
Since the early 2000s, numerous computational tools have been created and used to predict intrinsic disorder in proteins. At present, the output from these algorithms is difficult to interpret in the absence of standards or references for comparison. There are many reasons to establish a set of standard-based guidelines to evaluate computational protein disorder predictions. This viewpoint explores a handful of these reasons, including standardizing nomenclature to improve communication, rigor and reproducibility, and making it easier for newcomers to enter the field. An approach for reporting predicted disorder in single proteins with respect to whole proteomes is discussed. The suggestions …
Intrinsic Disorder And Posttranslational Modifications: The Darker Side Of The Biological Dark Matter, April L. Darling, Vladimir N. Uversky
Intrinsic Disorder And Posttranslational Modifications: The Darker Side Of The Biological Dark Matter, April L. Darling, Vladimir N. Uversky
Molecular Medicine Faculty Publications
Intrinsically disordered proteins (IDPs) and intrinsically disordered protein regions (IDPRs) are functional proteins and domains that devoid stable secondary and/or tertiary structure. IDPs/IDPRs are abundantly present in various proteomes, where they are involved in regulation, signaling, and control, thereby serving as crucial regulators of various cellular processes. Various mechanisms are utilized to tightly regulate and modulate biological functions, structural properties, cellular levels, and localization of these important controllers. Among these regulatory mechanisms are precisely controlled degradation and different posttranslational modifications (PTMs). Many normal cellular processes are associated with the presence of the right amounts of precisely activated IDPs at right …
Deciphering The Dark Proteome Of Chikungunya Virus, Ankur Singh, Ankur Kumar, Rakhi Yadav, Vladimir N. Uversky, Rajanish Giri
Deciphering The Dark Proteome Of Chikungunya Virus, Ankur Singh, Ankur Kumar, Rakhi Yadav, Vladimir N. Uversky, Rajanish Giri
Molecular Medicine Faculty Publications
Chikungunya virus (CHIKV) is a mosquito-borne alphavirus. The outbreak of CHIKV infection has been seen in many tropical and subtropical regions of the biosphere. Current reports evidenced that after outbreaks in 2005–06, the fitness of this virus propagating in Aedes albopictus enhanced due to the epistatic mutational changes in its envelope protein. In our study, we evaluated the prevalence of intrinsically disordered proteins (IDPs) and IDP regions (IDPRs) in CHIKV proteome. IDPs/IDPRs are known as members of a ‘Dark Proteome’ that defined as a set of polypeptide segments or whole protein without unique three-dimensional structure within the cellular milieu but …
Electronegativity And Intrinsic Disorder Of Preeclampsia-Related Proteins, Carlos Polanco, Jorge Alberto Castañón-González, Vladimir N. Uversky, Thomas Buhse, José Lino Mendoza, Juan J. Calva
Electronegativity And Intrinsic Disorder Of Preeclampsia-Related Proteins, Carlos Polanco, Jorge Alberto Castañón-González, Vladimir N. Uversky, Thomas Buhse, José Lino Mendoza, Juan J. Calva
Molecular Medicine Faculty Publications
Preeclampsia, hemorrhage, and infection are the leading causes of maternal death in underdeveloped countries. Since several proteins associated with preeclampsia are known, we conducted a computational study in which evaluated the commonness and potential functionality of intrinsic disorder in these proteins and also made an attempt to characterize their origin. To this end, we used a several supervised techniques, as a Polarity Index Method (PIM), which evaluates the electronegativity of proteins from their sequence alone. Peculiarities of resulting polar profile of the group of preeclampsia-related proteins were then compared with profiles of a group of lipoproteins, antimicrobial peptides, angiogenesis-related proteins, …
Calreticulin: Challenges Posed By The Intrinsically Disordered Nature Of Calreticulin To The Study Of Its Function, Lilian Varricchio, Mario Falchi, Massimiliano Dall'ora, Benedittis, Caterina De Benedittis, Alessandra Ruggeri, Vladimir N. Uversky, Anna Rita Migliaccio
Calreticulin: Challenges Posed By The Intrinsically Disordered Nature Of Calreticulin To The Study Of Its Function, Lilian Varricchio, Mario Falchi, Massimiliano Dall'ora, Benedittis, Caterina De Benedittis, Alessandra Ruggeri, Vladimir N. Uversky, Anna Rita Migliaccio
Molecular Medicine Faculty Publications
Calreticulin is a Ca2+-binding chaperone protein, which resides mainly in the endoplasmic reticulum but also found in other cellular compartments including the plasma membrane. In addition to Ca2+, calreticulin binds and regulates almost all proteins and most of the mRNAs deciding their intracellular fate. The potential functions of calreticulin are so numerous that identification of all of them is becoming a nightmare. Still the recent discovery that patients affected by the Philadelphia-negative myeloproliferative disorders essential thrombocytemia or primary myelofibrosis not harboring JAK2 mutations carry instead calreticulin mutations disrupting its C-terminal domain has highlighted the clinical need …
Functional Analysis Of Human Hub Proteins And Their Interactors Involved In The Intrinsic Disorder-Enriched Interactions, Gang Hu, Zhonghua Wu, Vladimir N. Uversky, Lukasz Kurgan
Functional Analysis Of Human Hub Proteins And Their Interactors Involved In The Intrinsic Disorder-Enriched Interactions, Gang Hu, Zhonghua Wu, Vladimir N. Uversky, Lukasz Kurgan
Molecular Medicine Faculty Publications
Some of the intrinsically disordered proteins and protein regions are promiscuous interactors that are involved in one-to-many and many-to-one binding. Several studies have analyzed enrichment of intrinsic disorder among the promiscuous hub proteins. We extended these works by providing a detailed functional characterization of the disorder-enriched hub protein-protein interactions (PPIs), including both hubs and their interactors, and by analyzing their enrichment among disease-associated proteins. We focused on the human interactome, given its high degree of completeness and relevance to the analysis of the disease-linked proteins. We quantified and investigated numerous functional and structural characteristics of the disorder-enriched hub PPIs, including …
Structure And Function Relationships Of Proteins Based On Polar Profile: A Review, Carlos Polanco, Thomas Buhse, Vladimir N. Uversky
Structure And Function Relationships Of Proteins Based On Polar Profile: A Review, Carlos Polanco, Thomas Buhse, Vladimir N. Uversky
Molecular Medicine Faculty Publications
Proteins in the post-genome era impose diverse research challenges, the main are the understanding of their structure-function mechanism, and the growing need for new pharmaceutical drugs, particularly antibiotics that help clinicians treat the ever- increasing number of Multidrug-Resistant Organisms (MDROs). Although, there is a wide range of mathematical-computational algorithms to satisfy the demand, among them the Quantitative Structure-Activity Relationship algorithms that have shown better performance using a characteristic training data of the property searched; their performance has stagnated regardless of the number of metrics they evaluate and their complexity. This article reviews the characteristics of these metrics, and the need …
Classifying Lipoproteins Based On Their Polar Profiles., Carlos Polanco, Jorge Alberto Castañón-González, Thomas Buhse, Vladimir N. Uversky, Rafael Zonana Amkie
Classifying Lipoproteins Based On Their Polar Profiles., Carlos Polanco, Jorge Alberto Castañón-González, Thomas Buhse, Vladimir N. Uversky, Rafael Zonana Amkie
Molecular Medicine Faculty Publications
No abstract provided.
Dancing Protein Clouds: The Strange Biology And Chaotic Physics Of Intrinsically Disordered Proteins, Vladimir N. Uversky
Dancing Protein Clouds: The Strange Biology And Chaotic Physics Of Intrinsically Disordered Proteins, Vladimir N. Uversky
Molecular Medicine Faculty Publications
Biologically active but floppy proteins represent a new reality of modern protein science. These intrinsically disordered proteins (IDPs) and hybrid proteins containing ordered and intrinsically disordered protein regions (IDPRs) constitute a noticeable part of any given proteome. Functionally, they complement ordered proteins, and their conformational flexibility and structural plasticity allow them to perform impossible tricks and be engaged in biological activities that are inaccessible to well folded proteins with their unique structures. The major goals of this minireview are to show that, despite their simplified amino acid sequences, IDPs/IDPRs are complex entities often resembling chaotic systems, are structurally and functionally …
Intrinsically Disordered Proteins And Their (Disordered) Proteomes In Neurodegenerative Disorders, Vladimir N. Uversky
Intrinsically Disordered Proteins And Their (Disordered) Proteomes In Neurodegenerative Disorders, Vladimir N. Uversky
Molecular Medicine Faculty Publications
No abstract provided.
Identification Of Proteins Associated With Amyloidosis By Polarity Index Method., Carlos Polanco, José Lino Samaniego, Vladimir N N. Uversky, Jorge Alberto Castañón-González, Thomas Buhse, Marili Leopold-Sordo, Alejandro Madero-Arteaga, Alicia Morales-Reyes, Lourdes Tavera-Sierra, Jesus A. González-Bernal, Miguel Arias-Estrada
Identification Of Proteins Associated With Amyloidosis By Polarity Index Method., Carlos Polanco, José Lino Samaniego, Vladimir N N. Uversky, Jorge Alberto Castañón-González, Thomas Buhse, Marili Leopold-Sordo, Alejandro Madero-Arteaga, Alicia Morales-Reyes, Lourdes Tavera-Sierra, Jesus A. González-Bernal, Miguel Arias-Estrada
Molecular Medicine Faculty Publications
There is a natural protein form, insoluble and resistant to proteolysis, adopted by many proteins independently of their amino acid sequences via specific misfolding-aggregation process. This dynamic process occurs in parallel with or as an alternative to physiologic folding, generating toxic protein aggregates that are deposited and accumulated in various organs and tissues. These proteinaceous deposits typically represent bundles of β-sheet-enriched fibrillar species known as the amyloid fibrils that are responsible for serious pathological conditions, including but not limited to neurodegenerative diseases, grouped under the term amyloidoses. The proteins that might adopt this fibrillar conformation are some globular proteins and …
Intrinsically Disordered Proteins In The Nucleus Of Human Cells, Telma Frege, Vladimir N. Uversky
Intrinsically Disordered Proteins In The Nucleus Of Human Cells, Telma Frege, Vladimir N. Uversky
Molecular Medicine Faculty Publications
Intrinsically disordered proteins are known to perform a variety of important functions such as macromolecular recognition, promiscuous binding, and signaling. They are crucial players in various cellular pathway and processes, where they often have key regulatory roles. Among vital cellular processes intimately linked to the intrinsically disordered proteins is transcription, an intricate biological performance predominantly developing inside the cell nucleus. With this work, we gathered information about proteins that exist in various compartments and sub-nuclear bodies of the nucleus of the human cells, with the goal of identifying which ones are highly disordered and which functions are ascribed to the …