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A Widely Employed Germ Cell Marker Is An Ancient Disordered Protein With Reproductive Functions In Diverse Eukaryotes, Michelle A. Carmell, Gregoriy A. Dokshin, Helen Skaletsky, Yueh-Chiang Hu, Josien C. Van Wolfswinkel, Kyomi J. Igarashi, Daniel W. Bellott, Michael Nefedov, Peter W. Reddien, George C. Enders, Vladimir N. Uversky, Craig C. Mello, David C. Page Jan 2016

A Widely Employed Germ Cell Marker Is An Ancient Disordered Protein With Reproductive Functions In Diverse Eukaryotes, Michelle A. Carmell, Gregoriy A. Dokshin, Helen Skaletsky, Yueh-Chiang Hu, Josien C. Van Wolfswinkel, Kyomi J. Igarashi, Daniel W. Bellott, Michael Nefedov, Peter W. Reddien, George C. Enders, Vladimir N. Uversky, Craig C. Mello, David C. Page

Molecular Medicine Faculty Publications

The advent of sexual reproduction and the evolution of a dedicated germline in multicellular organisms are critical landmarks in eukaryotic evolution. We report an ancient family of GCNA (germ cell nuclear antigen) proteins that arose in the earliest eukaryotes, and feature a rapidly evolving intrinsically disordered region (IDR). Phylogenetic analysis reveals that GCNA proteins emerged before the major eukaryotic lineages diverged; GCNA predates the origin of a dedicated germline by a billion years. Gcna gene expression is enriched in reproductive cells across eukarya – either just prior to or during meiosis in single-celled eukaryotes, and in stem cells and germ …


Order, Disorder, And Everything In Between, Shelly Deforte, Vladimir N. Uversky Jan 2016

Order, Disorder, And Everything In Between, Shelly Deforte, Vladimir N. Uversky

Molecular Medicine Faculty Publications

In addition to the “traditional” proteins characterized by the unique crystal-like structures needed for unique functions, it is increasingly recognized that many proteins or protein regions (collectively known as intrinsically disordered proteins (IDPs) and intrinsically disordered protein regions (IDPRs)), being biologically active, do not have a specific 3D-structure in their unbound states under physiological conditions. There are also subtler categories of disorder, such as conditional (or dormant) disorder and partial disorder. Both the ability of a protein/region to fold into a well-ordered functional unit or to stay intrinsically disordered but functional are encoded in the amino acid sequence. Structurally, IDPs/IDPRs …


Peculiarities Of The Super-Folder Gfp Folding In A Crowded Milieu, Olesia V. Stepanenko, Olga V. Stepanenko, Irina M. Kuznetsova, Vladimir N. Uversky, Konstantin K. Turoverov Jan 2016

Peculiarities Of The Super-Folder Gfp Folding In A Crowded Milieu, Olesia V. Stepanenko, Olga V. Stepanenko, Irina M. Kuznetsova, Vladimir N. Uversky, Konstantin K. Turoverov

Molecular Medicine Faculty Publications

The natural cellular milieu is crowded by large quantities of various biological macromolecules. This complex environment is characterized by a limited amount of unoccupied space, limited amounts of free water, and changed solvent properties. Obviously, such a tightly packed cellular environment is poorly mimicked by traditional physiological conditions, where low concentrations of a protein of interest are analyzed in slightly salted aqueous solutions. An alternative is given by the use of a model crowded milieu, where a protein of interest is immersed in a solution containing high concentrations of various polymers that serve as model crowding agents. An expected outcome …


Structure And Stability Of Recombinant Bovine Odorant-Binding Protein: Iii. Peculiarities Of The Wild Type Bobp Unfolding In Crowded Milieu, Olga V. Stepanenko, Denis O. Roginskii, Olesya V. Stepanenko, Irina M. Kuznetsova, Vladimir N. Uversky, Konstantin K. Turoverov Jan 2016

Structure And Stability Of Recombinant Bovine Odorant-Binding Protein: Iii. Peculiarities Of The Wild Type Bobp Unfolding In Crowded Milieu, Olga V. Stepanenko, Denis O. Roginskii, Olesya V. Stepanenko, Irina M. Kuznetsova, Vladimir N. Uversky, Konstantin K. Turoverov

Molecular Medicine Faculty Publications

Contrary to the majority of the members of the lipocalin family, which are stable monomers with the specific OBP fold (a β-barrel consisting of a 8-stranded anti-parallel β-sheet followed by a short α-helical segment, a ninth β-strand, and a disordered C-terminal tail) and a conserved disulfide bond, bovine odorant-binding protein (bOBP) does not have such a disulfide bond and forms a domain-swapped dimer that involves crossing the α-helical region from each monomer over the β-barrel of the other monomer. Furthermore, although natural bOBP isolated from bovine tissues exists as a stable domain-swapped dimer, recombinant bOBP has decreased dimerization potential and …


A Widely Employed Germ Cell Marker Is An Ancient Disordered Protein With Reproductive Functions In Diverse Eukaryotes, Michelle A. Carmell, Gregoriy A. Dokshin, Helen Skaletsky, Yueh-Chiang Hu, Josien C. Van Wolfswinkel, Kyomi J. Igarashi, Daniel W. Bellott, Michael Nefedov, Peter W. Reddien, George C. Enders, Vladimir N. Uversky, Craig C. Mello, David C. Page Jan 2016

A Widely Employed Germ Cell Marker Is An Ancient Disordered Protein With Reproductive Functions In Diverse Eukaryotes, Michelle A. Carmell, Gregoriy A. Dokshin, Helen Skaletsky, Yueh-Chiang Hu, Josien C. Van Wolfswinkel, Kyomi J. Igarashi, Daniel W. Bellott, Michael Nefedov, Peter W. Reddien, George C. Enders, Vladimir N. Uversky, Craig C. Mello, David C. Page

Molecular Medicine Faculty Publications

The advent of sexual reproduction and the evolution of a dedicated germline in multicellular organisms are critical landmarks in eukaryotic evolution. We report an ancient family of GCNA (germ cell nuclear antigen) proteins that arose in the earliest eukaryotes, and feature a rapidly evolving intrinsically disordered region (IDR). Phylogenetic analysis reveals that GCNA proteins emerged before the major eukaryotic lineages diverged; GCNA predates the origin of a dedicated germline by a billion years. Gcna gene expression is enriched in reproductive cells across eukarya – either just prior to or during meiosis in single-celled eukaryotes, and in stem cells and germ …


Structure And Stability Of Recombinant Bovine Odorant-Binding Protein: Ii. Unfolding Of The Monomeric Forms, Olga V. Stepanenko, Denis O. Roginski, Olesya V. Stepanenko, Irina M. Kuznetsova, Vladimir N. Uversky, Konstantin K. Turoverov Jan 2016

Structure And Stability Of Recombinant Bovine Odorant-Binding Protein: Ii. Unfolding Of The Monomeric Forms, Olga V. Stepanenko, Denis O. Roginski, Olesya V. Stepanenko, Irina M. Kuznetsova, Vladimir N. Uversky, Konstantin K. Turoverov

Molecular Medicine Faculty Publications

In a family of monomeric odorant-binding proteins (OBPs), bovine OBP (bOBP), that lacks conserved disulfide bond found in other OBPs, occupies unique niche because of its ability to form domain-swapped dimers. In this study, we analyzed conformational stabilities of the recombinant bOBP and its monomeric variants, the bOBP-Gly121+ mutant containing an additional glycine residue after the residue 121 of the bOBP, and the GCC-bOBP mutant obtained from the bOBP-Gly121+ form by introduction of the Trp64Cys/His155Cys double mutation to restore the canonical disulfide bond. We also analyzed the effect of the natural ligand binding on the conformational stabilities of these bOBP …


Smoking Correlates With Increased Cytoskeletal Protein-Related Coding Region Mutations In The Lung And Head And Neck Datasets Of The Cancer Genome Atlas, John M. Yavorski, George Blanck Jan 2016

Smoking Correlates With Increased Cytoskeletal Protein-Related Coding Region Mutations In The Lung And Head And Neck Datasets Of The Cancer Genome Atlas, John M. Yavorski, George Blanck

Molecular Medicine Faculty Publications

Cancer from smoking tobacco is considered dependent on mutagens, but significant molecular aspects of smoking-specific, cancer development remain unknown. We defined sets of coding regions for oncoproteins, tumor suppressor proteins, and cytoskeletal-related proteins that were compared between nonsmokers and smokers, for mutation occurrences, in the lung adenocarcinoma (LUAD), head and neck squamous carcinoma (HNSC), bladder carcinoma (BLCA), and pancreatic adenocarcinoma ( PAAD) datasets from the cancer genome atlas (TCGA). We uncovered significant differences in overall mutation rates, and in mutation rates in cytoskeletal protein-related coding regions (CPCRs, including extracellular matrix protein coding regions), between nonsmokers and smokers in LUAD and …


Detection Of Productively Rearranged Tcr-Α V–J Sequences In Tcga Exome Files: Implications For Tumor Immunoscoring And Recovery Of Antitumor T-Cells, Thomas R. Gill, Mohammad D. Samy, Shanitra N. Butler, James A. Mauro, Wade J. Sexton, George Blanck Jan 2016

Detection Of Productively Rearranged Tcr-Α V–J Sequences In Tcga Exome Files: Implications For Tumor Immunoscoring And Recovery Of Antitumor T-Cells, Thomas R. Gill, Mohammad D. Samy, Shanitra N. Butler, James A. Mauro, Wade J. Sexton, George Blanck

Molecular Medicine Faculty Publications

Tumor immunoscoring is rapidly becoming a universal parameter of prognosis, and T-cells isolated from tumor masses are used for ex vivo amplification and readministration to patients to facilitate an antitumor immune response. We recently exploited the cancer genome atlas (TCGA) RNASeq data to assess T-cell receptor (TcR) expression and, in particular, discovered strong correlations between major histocompatibility class II (MHCII) and TcR-α constant region expression levels. In this article, we describe the results of searching TCGA exome files for TcR-α V-regions, followed by searching the V-region datasets for TcR-α-J regions. Both primary and metastatic breast cancer sample files contained recombined …


Yersinia Pestis Caf1 Protein: Effect Of Sequence Polymorphism On Intrinsic Disorder Propensity, Serological Cross-Reactivity And Cross-Protectivity Of Isoforms, Pavel Kh. Kopylov, Mikhail E. Platonov, Vitaly G. Ablamunits, Tat’Yana I. Kombarova, Sergey A. Ivanov, Lidiya A. Kadnikova, Aleksey N. Somov, Svetlana V. Dentovskaya, Vladimir N. Uversky, Andrey P. Anisimov Jan 2016

Yersinia Pestis Caf1 Protein: Effect Of Sequence Polymorphism On Intrinsic Disorder Propensity, Serological Cross-Reactivity And Cross-Protectivity Of Isoforms, Pavel Kh. Kopylov, Mikhail E. Platonov, Vitaly G. Ablamunits, Tat’Yana I. Kombarova, Sergey A. Ivanov, Lidiya A. Kadnikova, Aleksey N. Somov, Svetlana V. Dentovskaya, Vladimir N. Uversky, Andrey P. Anisimov

Molecular Medicine Faculty Publications

Yersinia pestis Caf1 is a multifunctional protein responsible for antiphagocytic activity and is a key protective antigen. It is generally conserved between globally distributed Y. pestis strains, but Y. pestis subsp. microtus biovar caucasica strains circulating within populations of common voles in Georgia and Armenia were reported to carry a single substitution of alanine to serine. We investigated polymorphism of the Caf1 sequences among other Y. pestis subsp. microtus strains, which have a limited virulence in guinea pigs and in humans. Sequencing of caf1 genes from 119 Y. pestis strains belonging to different biovars within subsp. microtus showed that the …


A Hyperbranched Dopamine-Containing Peg-Based Polymer For The Inhibition Of Α-Synuclein Fibrillation, Leonid Breydo, Ben Newland, Hong Zhang, Anne Rosser, Carsten Werner, Vladimir N. Uversky, Wenxin Wang Jan 2016

A Hyperbranched Dopamine-Containing Peg-Based Polymer For The Inhibition Of Α-Synuclein Fibrillation, Leonid Breydo, Ben Newland, Hong Zhang, Anne Rosser, Carsten Werner, Vladimir N. Uversky, Wenxin Wang

Molecular Medicine Faculty Publications

Aggregation of α-synuclein is believed to play an important role in Parkinson's disease and in other neurodegenerative maladies. Small molecule inhibitors of this process are among the most promising drug candidates for neurodegenerative diseases. Dendrimers have also been studied for anti-fibrillation applications but they can be difficult and expensive to synthetize. Here we show that RAFT polymerization can be used to produce a hyperbranched polyethylene glycol structure via a one-pot reaction. This polymer included a dopamine moiety, a known inhibitor of α-synuclein fibril formation. Dopamine within the polymer structure was capable of aggregation inhibition, although not to the same degree …


Structure And Stability Of Recombinant Bovine Odorant-Binding Protein: Ii. Unfolding Of The Monomeric Forms, Olga V. Stepanenko, Denis O. Roginskii, Olesya V. Stepanenko, Irina M. Kuznetsova, Vladimir N. Uversky, Konstantin K. Turoverov Jan 2016

Structure And Stability Of Recombinant Bovine Odorant-Binding Protein: Ii. Unfolding Of The Monomeric Forms, Olga V. Stepanenko, Denis O. Roginskii, Olesya V. Stepanenko, Irina M. Kuznetsova, Vladimir N. Uversky, Konstantin K. Turoverov

Molecular Medicine Faculty Publications

In a family of monomeric odorant-binding proteins (OBPs), bovine OBP (bOBP), that lacks conserved disulfide bond found in other OBPs, occupies unique niche because of its ability to form domain-swapped dimers. In this study, we analyzed conformational stabilities of the recombinant bOBP and its monomeric variants, the bOBP-Gly121+ mutant containing an additional glycine residue after the residue 121 of the bOBP, and the GCC-bOBP mutant obtained from the bOBP-Gly121+ form by introduction of the Trp64Cys/His155Cys double mutation to restore the canonical disulfide bond. We also analyzed the effect of the natural ligand binding on the conformational stabilities of these bOBP …


Prothymosin-Α Variants Elicit Anti-Hiv-1 Response Via Tlr4 Dependent And Independent Pathways, G. Luca Gusella, Avelino Teixeira, Judith Aberg, Vladimir N. Uversky, Arevik Mosoian Jan 2016

Prothymosin-Α Variants Elicit Anti-Hiv-1 Response Via Tlr4 Dependent And Independent Pathways, G. Luca Gusella, Avelino Teixeira, Judith Aberg, Vladimir N. Uversky, Arevik Mosoian

Molecular Medicine Faculty Publications

Prothymosin α (ProTα) (isoform 2: iso2) is a widely distributed, small acidic protein with intracellular and extracellular-associated functions. Recently, we identified two new ProTα variants with potent anti-HIV activity from CD8+ T cells and cervicovaginal lavage. The first is a splice variant of the ProTα gene known as isoB and the second is the product of ProTα pseudogene 7 (p7). Similarly to iso2, the anti-HIV activity of both variants is mediated by type I IFN. Here we tested whether the immunomodulatory activity of isoB and p7 are also TLR4 dependent and determined their kinetic of release in response to HIV-1 …


Structure And Stability Of Recombinant Bovine Odorant-Binding Protein: I. Design And Analysis Of Monomeric Mutants, Olga V. Stepanenko, Denis O. Roginskii, Olesya V. Stepanenko, Irina M. Kuznetsova, Vladimir N. Uversky, Konstantin K. Turoverov Jan 2016

Structure And Stability Of Recombinant Bovine Odorant-Binding Protein: I. Design And Analysis Of Monomeric Mutants, Olga V. Stepanenko, Denis O. Roginskii, Olesya V. Stepanenko, Irina M. Kuznetsova, Vladimir N. Uversky, Konstantin K. Turoverov

Molecular Medicine Faculty Publications

Bovine odorant-binding protein (bOBP) differs from other lipocalins by lacking the conserved disulfide bond and for being able to form the domain-swapped dimers. To identify structural features responsible for the formation of the bOBP unique dimeric structure and to understand the role of the domain swapping on maintaining the native structure of the protein, structural properties of the recombinant wild type bOBP and its mutant that cannot dimerize via the domain swapping were analyzed. We also looked at the effect of the disulfide bond by designing a monomeric bOBPs with restored disulfide bond which is conserved in other lipocalins. Finally, …


Structure And Function Relationships Of Proteins Based On Polar Profile: A Review, Carlos Polanco, Thomas Buhse, Vladimir N. Uversky Jan 2016

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 …


Looking At The Carcinogenicity Of Human Insulin Analogues Via The Intrinsic Disorder Prism, Elrashdy M. Redwan, Moustafa H. Linjawi, Vladimir N. Uversky Jan 2016

Looking At The Carcinogenicity Of Human Insulin Analogues Via The Intrinsic Disorder Prism, Elrashdy M. Redwan, Moustafa H. Linjawi, Vladimir N. Uversky

Molecular Medicine Faculty Publications

Therapeutic insulin, in its native and biosynthetic forms as well as several currently available insulin analogues, continues to be the protein of most interest to researchers. From the time of its discovery to the development of modern insulin analogues, this important therapeutic protein has passed through several stages and product generations. Beside the well-known link between diabetes and cancer risk, the currently used therapeutic insulin analogues raised serious concerns due to their potential roles in cancer initiation and/or progression. It is possible that structural variations in some of the insulin analogues are responsible for the appearance of new oncogenic species …


Compartmentalization And Functionality Of Nuclear Disorder: Intrinsic Disorder And Protein-Protein Interactions In Intra-Nuclear Compartments, Fanchi Meng, Insung Na, Lukasz Kurgan, Vladimir N. Uversky Jan 2016

Compartmentalization And Functionality Of Nuclear Disorder: Intrinsic Disorder And Protein-Protein Interactions In Intra-Nuclear Compartments, Fanchi Meng, Insung Na, Lukasz Kurgan, Vladimir N. Uversky

Molecular Medicine Faculty Publications

The cell nucleus contains a number of membrane-less organelles or intra-nuclear compartments. These compartments are dynamic structures representing liquid-droplet phases which are only slightly denser than the bulk intra-nuclear fluid. They possess different functions, have diverse morphologies, and are typically composed of RNA (or, in some cases, DNA) and proteins. We analyzed 3005 mouse proteins localized in specific intra-nuclear organelles, such as nucleolus, chromatin, Cajal bodies, nuclear speckles, promyelocytic leukemia (PML) nuclear bodies, nuclear lamina, nuclear pores, and perinuclear compartment and compared them with ~29,863 non-nuclear proteins from mouse proteome. Our analysis revealed that intrinsic disorder is enriched in the …


Two Isoforms Of Yersinia Pestis Plasminogen Activator Pla: Intraspecies Distribution, Intrinsic Disorder Propensity, And Contribution To Virulence, Svetlana V. Dentovskaya, Mikhail E. Platonov, Tat’Yana E. Svetoch, Pavel Kh. Kopylov, Tat’Yana I. Kombarova, Sergey A. Ivanov, Rima Z. Shaikhutdinova, Lyubov’ V. Kolombet, Sadhana Chauhan, Vitaly G. Ablamunits, Vladimir L. Motin, Vladimir N. Uversky, Andrey P. Anisimov Jan 2016

Two Isoforms Of Yersinia Pestis Plasminogen Activator Pla: Intraspecies Distribution, Intrinsic Disorder Propensity, And Contribution To Virulence, Svetlana V. Dentovskaya, Mikhail E. Platonov, Tat’Yana E. Svetoch, Pavel Kh. Kopylov, Tat’Yana I. Kombarova, Sergey A. Ivanov, Rima Z. Shaikhutdinova, Lyubov’ V. Kolombet, Sadhana Chauhan, Vitaly G. Ablamunits, Vladimir L. Motin, Vladimir N. Uversky, Andrey P. Anisimov

Molecular Medicine Faculty Publications

It has been shown previously that several endemic Y. pestis isolates with limited virulence contained the I259 isoform of the outer membrane protease Pla, while the epidemic highly virulent strains possessed only the T259 Pla isoform. Our sequence analysis of the pla gene from 118 Y. pestis subsp. microtus strains revealed that the I259 isoform was present exclusively in the endemic strains providing a convictive evidence of more ancestral origin of this isoform. Analysis of the effects of the I259T polymorphism on the intrinsic disorder propensity of Pla revealed that the I259T mutation slightly increases the intrinsic disorder propensity of …


Expression, Purification, And Characterization Of Interleukin-11 Orthologues, Andrei S. Sokolov, Alexei S. Kazakov, Valery V. Solovyev, Ramis G. Ismailov, Vladimir N. Uversky, Yulia S. Lapteva, Roman V. Mikhailov, Ekaterina V. Pavlova, Iana O. Terletskaya, Ludmila V. Ermolina, Sergei E. Permyakov, Eugene A. Permyakov, Eugene A. Permyakov Jan 2016

Expression, Purification, And Characterization Of Interleukin-11 Orthologues, Andrei S. Sokolov, Alexei S. Kazakov, Valery V. Solovyev, Ramis G. Ismailov, Vladimir N. Uversky, Yulia S. Lapteva, Roman V. Mikhailov, Ekaterina V. Pavlova, Iana O. Terletskaya, Ludmila V. Ermolina, Sergei E. Permyakov, Eugene A. Permyakov, Eugene A. Permyakov

Molecular Medicine Faculty Publications

Interleukin-11 (IL-11) is a multifunctional cytokine implicated in several normal and pathological processes. The decoding of IL-11 function and development of IL-11-targeted drugs dictate the use of laboratory animals and need of the better understanding of species specificity of IL-11 signaling. Here, we present a method for the recombinant interleukin-11 (rIL-11) production from the important model animals, mouse and macaque. The purified mouse and macaque rIL-11 interact with extracellular domain of human IL-11 receptor subunit α and activate STAT3 signaling in HEK293 cells co-expressing human IL-11 receptors with efficacies resembling those of human rIL-11. Hence, the evolutionary divergence does not …


Simple Approach For Ranking Structure Determining Residues, Oscar D. Luna-Martínez, Abraham Vidal-Limón, Miryam I. Villalba-Velázquez, Rosalba Sánchez-Alcalá, Ramón Garduño-Juárez, Vladimir N. Uversky, Baltazar Becerril Jan 2016

Simple Approach For Ranking Structure Determining Residues, Oscar D. Luna-Martínez, Abraham Vidal-Limón, Miryam I. Villalba-Velázquez, Rosalba Sánchez-Alcalá, Ramón Garduño-Juárez, Vladimir N. Uversky, Baltazar Becerril

Molecular Medicine Faculty Publications

Mutating residues has been a common task in order to study structural properties of the protein of interest. Here, we propose and validate a simple method that allows the identification of structural determinants; i.e., residues essential for preservation of the stability of global structure, regardless of the protein topology. This method evaluates all of the residues in a 3D structure of a given globular protein by ranking them according to their connectivity and movement restrictions without topology constraints. Our results matched up with sequence-based predictors that look up for intrinsically disordered segments, suggesting that protein disorder can also be described …


Classifying Lipoproteins Based On Their Polar Profiles., Carlos Polanco, Jorge Alberto Castañón-González, Thomas Buhse, Vladimir N. Uversky, Rafael Zonana Amkie Jan 2016

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.


Intrinsically Disordered Side Of The Zika Virus Proteome, Rajanish Giri, Deepak Kumar, Nitin Sharma, Vladimir N. Uversky Jan 2016

Intrinsically Disordered Side Of The Zika Virus Proteome, Rajanish Giri, Deepak Kumar, Nitin Sharma, Vladimir N. Uversky

Molecular Medicine Faculty Publications

Over the last few decades, concepts of protein intrinsic disorder have been implicated in different biological processes. Recent studies have suggested that intrinsically disordered proteins (IDPs) provide structural plasticity and functional diversity to viral proteins that are involved in rapid replication and immune evasion in host cells. In case of Zika virus, the roles of protein intrinsic disorder in mechanisms of pathogenesis are not completely understood. In this study, we have analyzed the prevalence of intrinsic disorder in Zika virus proteome (strain MR 766). Our analyses revealed that Zika virus polyprotein is enriched with intrinsically disordered protein regions (IDPRs) and …


Dancing Protein Clouds: The Strange Biology And Chaotic Physics Of Intrinsically Disordered Proteins, Vladimir N. Uversky Jan 2016

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 …