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Articles 1 - 22 of 22
Full-Text Articles in Medicine and Health Sciences
Liquid–Liquid Phase Separation By Intrinsically Disordered Protein Regions Of Viruses: Roles In Viral Life Cycle And Control Of Virus–Host Interactions, Stefania Brocca, Rita Grandori, Sonia Longhi, Vladimir N. Uversky
Liquid–Liquid Phase Separation By Intrinsically Disordered Protein Regions Of Viruses: Roles In Viral Life Cycle And Control Of Virus–Host Interactions, Stefania Brocca, Rita Grandori, Sonia Longhi, Vladimir N. Uversky
Molecular Medicine Faculty Publications
Intrinsically disordered proteins (IDPs) are unable to adopt a unique 3D structure under physiological conditions and thus exist as highly dynamic conformational ensembles. IDPs are ubiquitous and widely spread in the protein realm. In the last decade, compelling experimental evidence has been gathered, pointing to the ability of IDPs and intrinsically disordered regions (IDRs) to undergo liquid–liquid phase separation (LLPS), a phenomenon driving the formation of membrane-less organelles (MLOs). These biological condensates play a critical role in the spatio-temporal organization of the cell, where they exert a multitude of key biological functions, ranging from transcriptional regulation and silencing to control …
Rigidity Of The Outer Shell Predicted By A Protein Intrinsic Disorder Model Sheds Light On The Covid-19 (Wuhan-2019-Ncov) Infectivity, Gerard Kian-Meng Goh, A. Keith Dunker, James A. Foster, Vladimir N. Uversky
Rigidity Of The Outer Shell Predicted By A Protein Intrinsic Disorder Model Sheds Light On The Covid-19 (Wuhan-2019-Ncov) Infectivity, Gerard Kian-Meng Goh, A. Keith Dunker, James A. Foster, Vladimir N. Uversky
Molecular Medicine Faculty Publications
The world is currently witnessing an outbreak of a new coronavirus spreading quickly across China and affecting at least 24 other countries. With almost 65,000 infected, a worldwide death toll of at least 1370 (as of 14 February 2020), and with the potential to affect up to two-thirds of the world population, COVID-19 is considered by the World Health Organization (WHO) to be a global health emergency. The speed of spread and infectivity of COVID-19 (also known as Wuhan-2019-nCoV) are dramatically exceeding those of the Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus (SARS-CoV). In fact, …
Interferon Beta Activity Is Modulated Via Binding Of Specific S100 Proteins, Alexei S. Kazakov, Alexander D. Sofin, Nadezhda V. Avkhacheva, Alexander I. Denesyuk, Eugenia I. Deryusheva, Victoria A. Rastrygina, Andrey S. Sokolov, Maria E. Permyakova, Ekaterina A. Litus, Vladimir N. Uversky, Eugene A. Permyakov, Sergei E. Permyakov
Interferon Beta Activity Is Modulated Via Binding Of Specific S100 Proteins, Alexei S. Kazakov, Alexander D. Sofin, Nadezhda V. Avkhacheva, Alexander I. Denesyuk, 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
Interferon-β (IFN-β) is a pleiotropic cytokine used for therapy of multiple sclerosis, which is also effective in suppression of viral and bacterial infections and cancer. Recently, we reported a highly specific interaction between IFN-β and S100P lowering IFN-β cytotoxicity to cancer cells (Int J Biol Macromol. 2020; 143: 633–639). S100P is a member of large family of multifunctional Ca2+-binding proteins with cytokine-like activities. To probe selectivity of IFN-β—S100 interaction with respect to S100 proteins, we used surface plasmon resonance spectroscopy, chemical crosslinking, and crystal violet assay. Among the thirteen S100 proteins studied S100A1, S100A4, and S100A6 proteins exhibit strictly Ca2+-dependent …
Intrinsic Disorder-Based Design Of Stable Globular Proteins, Galina S. Nagibina, Bogdan S. Melnik, Vladimir N. Uversky, Tatiana N. Melnik, Bogdan S. Melnik
Intrinsic Disorder-Based Design Of Stable Globular Proteins, Galina S. Nagibina, Bogdan S. Melnik, Vladimir N. Uversky, Tatiana N. Melnik, Bogdan S. Melnik
Molecular Medicine Faculty Publications
Directed stabilization of globular proteins via substitution of a minimal number of amino acid residues is one of the most complicated experimental tasks. This work summarizes our research on the effect of amino acid substitutions on the protein stability utilizing the outputs of the analysis of intrinsic disorder predisposition of target proteins. This allowed us to formulate the basis of one of the possible approaches to the stabilization of globular proteins. The idea is quite simple. To stabilize a protein as a whole, one needs to find its "weakest spot" and stabilize it, but the question is how this weak …
Hsp22 With An N-Terminal Domain Truncation Mediates A Reduction In Tau Protein Levels, Jack M. Webster, April L. Darling, Taylor A. Sanders, Danielle M. Blazier, Yamile Vidal-Aguiar, David Beaulieu-Abdelahad, Drew G. Plemmons, Shannon E. Hill, Vladimir N. Uversky, Paula C. Bickford, Chad Anthony Dickey, Laura J. Blair
Hsp22 With An N-Terminal Domain Truncation Mediates A Reduction In Tau Protein Levels, Jack M. Webster, April L. Darling, Taylor A. Sanders, Danielle M. Blazier, Yamile Vidal-Aguiar, David Beaulieu-Abdelahad, Drew G. Plemmons, Shannon E. Hill, Vladimir N. Uversky, Paula C. Bickford, Chad Anthony Dickey, Laura J. Blair
Molecular Medicine Faculty Publications
Misfolding, aggregation and accumulation of proteins are toxic elements in the progression of a broad range of neurodegenerative diseases. Molecular chaperones enable a cellular defense by reducing or compartmentalizing these insults. Small heat shock proteins (sHsps) engage proteins early in the process of misfolding and can facilitate their proper folding or refolding, sequestration, or clearance. Here, we evaluate the effects of the sHsp Hsp22, as well as a pseudophosphorylated mutant and an N-terminal domain deletion (NTDΔ) variant on tau aggregation in vitro and tau accumulation and aggregation in cultured cells. Hsp22 wild-type (WT) protein had a significant inhibitory effect on …
Unstructured Biology Of Proteins From Ubiquitin-Proteasome System: Roles In Cancer And Neurodegenerative Diseases, Kundlik Gadhave, Prateek Kumar, Shivani K. Kapuganti, Vladimir N. Uversky, Rajanish Giri
Unstructured Biology Of Proteins From Ubiquitin-Proteasome System: Roles In Cancer And Neurodegenerative Diseases, Kundlik Gadhave, Prateek Kumar, Shivani K. Kapuganti, Vladimir N. Uversky, Rajanish Giri
Molecular Medicine Faculty Publications
The 26S proteasome is a large (~2.5 MDa) protein complex consisting of at least 33 different subunits and many other components, which form the ubiquitin proteasomal system (UPS), an ATP-dependent protein degradation system in the cell. UPS serves as an essential component of the cellular protein surveillance machinery, and its dysfunction leads to cancer, neurodegenerative and immunological disorders. Importantly, the functions and regulations of proteins are governed by the combination of ordered regions, intrinsically disordered protein regions (IDPRs) and molecular recognition features (MoRFs). The structure–function relationships of UPS components have not been identified completely; therefore, in this study, we have …
Drug Discovery Targeting The Disorder-To-Order Transition Regions Through The Conformational Diversity Mimicking And Statistical Analysis, Insung Na, Sungwoo Choi, Seung Han Son, Vladimir N. Uversky, Chul Geun Kim
Drug Discovery Targeting The Disorder-To-Order Transition Regions Through The Conformational Diversity Mimicking And Statistical Analysis, Insung Na, Sungwoo Choi, Seung Han Son, Vladimir N. Uversky, Chul Geun Kim
Molecular Medicine Faculty Publications
Intrinsically disordered proteins exist as highly dynamic conformational ensembles of diverse forms. However, the majority of virtual screening only focuses on proteins with defined structures. This means that computer-aided drug discovery is restricted. As a breakthrough, understanding the structural characteristics of intrinsically disordered proteins and its application can open the gate for unrestricted drug discovery. First, we segmented the target disorder-to-order transition region into a series of overlapping 20-amino-acid-long peptides. Folding prediction generated diverse conformations of these peptides. Next, we applied molecular docking, new evaluation score function, and statistical analysis. This approach successfully distinguished known compounds and their corresponding binding …
Intrinsic Disorder In Tetratricopeptide Repeat Proteins, Nathan W. Bibber, Cornelia Haerle, Roy Khalifa, Bin Xue, Vladimir N. Uversky
Intrinsic Disorder In Tetratricopeptide Repeat Proteins, Nathan W. Bibber, Cornelia Haerle, Roy Khalifa, Bin Xue, Vladimir N. Uversky
Molecular Medicine Faculty Publications
Among the realm of repeat containing proteins that commonly serve as “scaffolds” promoting protein-protein interactions, there is a family of proteins containing between 2 and 20 tetratricopeptide repeats (TPRs), which are functional motifs consisting of 34 amino acids. The most distinguishing feature of TPR domains is their ability to stack continuously one upon the other, with these stacked repeats being able to affect interaction with binding partners either sequentially or in combination. It is known that many repeat-containing proteins are characterized by high levels of intrinsic disorder, and that many protein tandem repeats can be intrinsically disordered. Furthermore, it seems …
Linear Relationships Between Partition Coefficients Of Different Organic Compounds And Proteins In Aqueous Two-Phase Systems Of Various Polymer And Ionic Compositions, Nuno R. Da Silva, Luisa A. Ferreira, Pedro P. Madeira, José A. Teixeira, Vladimir N. Uversky, Boris Y. Zaslavsky
Linear Relationships Between Partition Coefficients Of Different Organic Compounds And Proteins In Aqueous Two-Phase Systems Of Various Polymer And Ionic Compositions, Nuno R. Da Silva, Luisa A. Ferreira, Pedro P. Madeira, José A. Teixeira, Vladimir N. Uversky, Boris Y. Zaslavsky
Molecular Medicine Faculty Publications
Analysis of the partition coefficients of small organic compounds and proteins in different aqueous two-phase systems under widely varied ionic compositions shows that logarithms of partition coefficients for any three compounds or proteins or two organic compounds and one protein are linearly interrelated, although for protein(s) there are ionic compositions when the linear fit does not hold. It is suggested that the established interrelationships are due to cooperativity of different types of solute–solvent interactions in aqueous media. This assumption is confirmed by analysis of distribution coefficients of various drugs in octanol-buffer systems with varied ionic compositions of the buffer. Analysis …
Yersinia Outer Membrane Vesicles As Potential Vaccine Candidates In Protecting Against Plague, Andrey A. Byvalov, Ilya V. Konyshev, Vladimir N. Uversky, Svetlana V. Dentovskaya, Andrey P. Anisimov
Yersinia Outer Membrane Vesicles As Potential Vaccine Candidates In Protecting Against Plague, Andrey A. Byvalov, Ilya V. Konyshev, Vladimir N. Uversky, Svetlana V. Dentovskaya, Andrey P. Anisimov
Molecular Medicine Faculty Publications
Despite the relatively low incidence of plague, its etiological agent, Yersinia pestis, is an exceptional epidemic danger due to the high infectivity and mortality of this infectious disease. Reports on the isolation of drug-resistant Y. pestis strains indicate the advisability of using asymmetric responses, such as phage therapy and vaccine prophylaxis in the fight against this problem. The current relatively effective live plague vaccine is not approved for use in most countries because of its ability to cause heavy local and system reactions and even a generalized infectious process in people with a repressed immune status or metabolic disorders, as …
Yersinia Pestis Plasminogen Activator, Florent Sebbane, Vladimir N. Uversky, Andrey P. Anisimov
Yersinia Pestis Plasminogen Activator, Florent Sebbane, Vladimir N. Uversky, Andrey P. Anisimov
Molecular Medicine Faculty Publications
The Gram-negative bacterium Yersinia pestis causes plague, a fatal flea-borne anthropozoonosis, which can progress to aerosol-transmitted pneumonia. Y. pestis overcomes the innate immunity of its host thanks to many pathogenicity factors, including plasminogen activator, Pla. This factor is a broad-spectrum outer membrane protease also acting as adhesin and invasin. Y. pestis uses Pla adhesion and proteolytic capacity to manipulate the fibrinolytic cascade and immune system to produce bacteremia necessary for pathogen transmission via fleabite or aerosols. Because of microevolution, Y. pestis invasiveness has increased significantly after a single amino-acid substitution (I259T) in Pla of one of the oldest Y. pestis …
Mmtr/Dmap1 Sets The Stage For Early Lineage Commitment Of Embryonic Stem Cells By Crosstalk With Pcg Proteins, Young Jin Lee, Seung Han Son, Chang Su Lim, Si Woo Lee, Sangwoon Lee, Jinseon Jeon, Dae Hyun Ha, Na Rae Jung, Su Youne Han, Byung-Rok Do, Insung Na, Vladimir N. Uversky, Chul Geun Kim
Mmtr/Dmap1 Sets The Stage For Early Lineage Commitment Of Embryonic Stem Cells By Crosstalk With Pcg Proteins, Young Jin Lee, Seung Han Son, Chang Su Lim, Si Woo Lee, Sangwoon Lee, Jinseon Jeon, Dae Hyun Ha, Na Rae Jung, Su Youne Han, Byung-Rok Do, Insung Na, Vladimir N. Uversky, Chul Geun Kim
Molecular Medicine Faculty Publications
Chromatin remodeling, including histone modification, chromatin (un)folding, and nucleosome remodeling, is a significant transcriptional regulation mechanism. By these epigenetic modifications, transcription factors and their regulators are recruited to the promoters of target genes, and thus gene expression is controlled through either transcriptional activation or repression. The Mat1-mediated transcriptional repressor (MMTR)/DNA methyltransferase 1 (DNMT1)-associated protein (Dmap1) is a transcription corepressor involved in chromatin remodeling, cell cycle regulation, DNA double-strand break repair, and tumor suppression. The Tip60-p400 complex proteins, including MMTR/Dmap1, interact with the oncogene Myc in embryonic stem cells (ESCs). These proteins interplay with the stem cell-related proteome networks and regulate …
Why Covid-19 Transmission Is More Efficient And Aggressive Than Viral Transmission In Previous Coronavirus Epidemics?, Fatma Elrashdy, Elrashdy M. Redwan, Vladimir N. Uversky
Why Covid-19 Transmission Is More Efficient And Aggressive Than Viral Transmission In Previous Coronavirus Epidemics?, Fatma Elrashdy, Elrashdy M. Redwan, Vladimir N. Uversky
Molecular Medicine Faculty Publications
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is causing a pandemic of coronavirus disease 2019 (COVID-19). The worldwide transmission of COVID-19 from human to human is spreading like wildfire, affecting almost every country in the world. In the past 100 years, the globe did not face a microbial pandemic similar in scale to COVID-19. Taken together, both previous outbreaks of other members of the coronavirus family (severe acute respiratory syndrome (SARS-CoV) and middle east respiratory syndrome (MERS-CoV)) did not produce even 1% of the global harm already inflicted by COVID-19. There are also four other CoVs capable of infecting humans …
The Pathophysiological Significance Of Fibulin-3, Imogen Livingstone, Vladimir N. Uversky, Dominic Furniss, Akira Wiberg
The Pathophysiological Significance Of Fibulin-3, Imogen Livingstone, Vladimir N. Uversky, Dominic Furniss, Akira Wiberg
Molecular Medicine Faculty Publications
Fibulin-3 (also known as EGF-containing fibulin extracellular matrix protein 1 (EFEMP1)) is a secreted extracellular matrix glycoprotein, encoded by the EFEMP1 gene that belongs to the eight-membered fibulin protein family. It has emerged as a functionally unique member of this family, with a diverse array of pathophysiological associations predominantly centered on its role as a modulator of extracellular matrix (ECM) biology. Fibulin-3 is widely expressed in the human body, especially in elastic-fibre-rich tissues and ocular structures, and interacts with enzymatic ECM regulators, including tissue inhibitor of metalloproteinase-3 (TIMP-3). A point mutation in EFEMP1 causes an inherited early-onset form of macular …
Lung Cancer Cells Survive Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Exposure Through Upregulation Of Cholesterol Synthesis, Mark C. Howell, Ryan Green, Roukiah Khalil, Elspeth Foran, Waise Quarni, Rajesh Nair, Stanley Stevens, Aleksandr Grinchuk, Andrew Hanna, Shyam Mohapatra, Subhra Mohapatra
Lung Cancer Cells Survive Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Exposure Through Upregulation Of Cholesterol Synthesis, Mark C. Howell, Ryan Green, Roukiah Khalil, Elspeth Foran, Waise Quarni, Rajesh Nair, Stanley Stevens, Aleksandr Grinchuk, Andrew Hanna, Shyam Mohapatra, Subhra Mohapatra
Molecular Medicine Faculty Publications
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) provide clinical benefits over chemotherapy for lung cancer patients with EGFR activating mutations. Despite initial clinical responses, long-term efficacy is not possible because of acquired resistance to these therapies. We have developed EGFR TKI drug-tolerant (DT) human lung cancer cell lines as a model for de novo resistance. Mass spectroscopic analysis revealed that the cytochrome P450 protein, CYP51A1 (Lanosterol 14α-demethylase), which is directly involved with cholesterol synthesis, was significantly upregulated in the DT cells. Total cellular cholesterol, and more specifically, mitochondrial cholesterol, were found to be upregulated in DT cells. We …
Proceedings Of The 2019 Nanoflorida International Conference Held At The University Of South Florida, Tampa, Fl, Shyam S. Mohapatra, Robert D. Frisina, Subhra Mohapatra, Mandip Singh, Manh-Huong Phan
Proceedings Of The 2019 Nanoflorida International Conference Held At The University Of South Florida, Tampa, Fl, Shyam S. Mohapatra, Robert D. Frisina, Subhra Mohapatra, Mandip Singh, Manh-Huong Phan
Molecular Medicine Faculty Publications
No abstract provided.
Why Covid-19 Transmission Is More Efficient And Aggressive Than Viral Transmission In Previous Coronavirus Epidemics?, Fatma Elrashdy, Elrashdy M. Redwan, Vladimir N. Uversky
Why Covid-19 Transmission Is More Efficient And Aggressive Than Viral Transmission In Previous Coronavirus Epidemics?, Fatma Elrashdy, Elrashdy M. Redwan, Vladimir N. Uversky
Molecular Medicine Faculty Publications
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is causing a pandemic of coronavirus disease 2019 (COVID-19). The worldwide transmission of COVID-19 from human to human is spreading like wildfire, affecting almost every country in the world. In the past 100 years, the globe did not face a microbial pandemic similar in scale to COVID-19. Taken together, both previous outbreaks of other members of the coronavirus family (severe acute respiratory syndrome (SARS-CoV) and middle east respiratory syndrome (MERS-CoV)) did not produce even 1% of the global harm already inflicted by COVID-19. There are also four other CoVs capable of infecting humans …
Granulins Modulate Liquid–Liquid Phase Separation And Aggregation Of The Prion-Like C-Terminal Domain Of The Neurodegeneration-Associated Protein Tdp-43, Anukool A. Bhopatkar, Vladimir N. Uversky, Vijayaraghavan Rangachari
Granulins Modulate Liquid–Liquid Phase Separation And Aggregation Of The Prion-Like C-Terminal Domain Of The Neurodegeneration-Associated Protein Tdp-43, Anukool A. Bhopatkar, Vladimir N. Uversky, Vijayaraghavan Rangachari
Molecular Medicine Faculty Publications
TAR DNA-binding protein 43 (TDP-43) has emerged as a key player in many neurodegenerative pathologies, including frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). Hallmarks of both FTLD and ALS are the toxic cytoplasmic inclusions of the prion-like C-terminal fragments of TDP-43 CTD (TDP-43 C-terminal domain), formed upon proteolytic cleavage of full-length TDP-43 in the nucleus and subsequent transport to the cytoplasm. Both full-length TDP-43 and its CTD are also known to form stress granules by coacervating with RNA in the cytoplasm during stress and may be involved in these pathologies. Furthermore, mutations in the PGRN gene, leading to …
The Dual Pi3kδ/Ck1Ε Inhibitor Umbralisib Exhibits Unique Immunomodulatory Effects On Cll T Cells, Kamira Maharaj, John J. Powers, Alex Achille, Melanie Mediavilla-Varela, Wael Gamal, Karen L. Burger, Renee Fonseca, Kun Jiang, Hari P. Miskin, Dave Maryanski, Andrii Monastyrskyi, Derek R. Duckett, William R. Roush, John L. Cleveland, Eva Sahakian, Javier Pinilla-Ibarz
The Dual Pi3kδ/Ck1Ε Inhibitor Umbralisib Exhibits Unique Immunomodulatory Effects On Cll T Cells, Kamira Maharaj, John J. Powers, Alex Achille, Melanie Mediavilla-Varela, Wael Gamal, Karen L. Burger, Renee Fonseca, Kun Jiang, Hari P. Miskin, Dave Maryanski, Andrii Monastyrskyi, Derek R. Duckett, William R. Roush, John L. Cleveland, Eva Sahakian, Javier Pinilla-Ibarz
Molecular Medicine Faculty Publications
The in-clinic phosphatidylinositol 3-kinase (PI3K) inhibitors idelalisib (CAL-101) and duvelisib (IPI-145) have demonstrated high rates of response and progression-free survival in clinical trials of B-cell malignancies, such as chronic lymphocytic leukemia (CLL). However, a high incidence of adverse events has led to frequent discontinuations, limiting the clinical development of these inhibitors. By contrast, the dual PI3Kδ/casein kinase-1-ε (CK1ε) inhibitor umbralisib (TGR-1202) also shows high rates of response in clinical trials but has an improved safety profile with fewer severe adverse events. Toxicities typical of this class of PI3K inhibitors are largely thought to be immune mediated, but they are poorly …
Relt Stains Prominently In B-Cell Lymphomas And Binds The Hematopoietic Transcription Factor Mdfic, John K. Cusick, Yasmeen Alhomsy, Stephanie Wong, George Talbott, Vladimir N. Uversky, Cara Hart, Nazila Hejazi, Aaron T. Jacobs, Yihui Shi
Relt Stains Prominently In B-Cell Lymphomas And Binds The Hematopoietic Transcription Factor Mdfic, John K. Cusick, Yasmeen Alhomsy, Stephanie Wong, George Talbott, Vladimir N. Uversky, Cara Hart, Nazila Hejazi, Aaron T. Jacobs, Yihui Shi
Molecular Medicine Faculty Publications
Receptor Expressed in Lymphoid Tissues (RELT) is a human tumor necrosis factor receptor superfamily member (TNFRSF) that is expressed most prominently in cells and tissues of the hematopoietic system. RELL1 and RELL2 are two homologs that physically interact with RELT and co-localize with RELT at the plasma membrane. This study sought to further elucidate the function of RELT by identifying novel protein interactions with RELT family members. The transcription factor MyoD family inhibitor domain-containing (MDFIC) was identified in a yeast two-hybrid genetic screen using RELL1 as bait. MDFIC co-localizes with RELT family members at the plasma membrane; this co-localization was …
Zooming Into The Dark Side Of Human Annexin-S100 Complexes: Dynamic Alliance Of Flexible Partners, Judith Weisz, Vladimir N. Uversky
Zooming Into The Dark Side Of Human Annexin-S100 Complexes: Dynamic Alliance Of Flexible Partners, Judith Weisz, Vladimir N. Uversky
Molecular Medicine Faculty Publications
Annexins and S100 proteins form two large families of Ca2+-binding proteins. They are quite different both structurally and functionally, with S100 proteins being small (10–12 kDa) acidic regulatory proteins from the EF-hand superfamily of Ca2+-binding proteins, and with annexins being at least three-fold larger (329 ± 12 versus 98 ± 7 residues) and using non-EF-hand-based mechanism for calcium binding. Members of both families have multiple biological roles, being able to bind to a large cohort of partners and possessing a multitude of functions. Furthermore, annexins and S100 proteins can interact with each other in either a Ca2+-dependent or Ca2+-independent manner, …
New Technologies To Analyse Protein Function: An Intrinsic Disorder Perspective, Vladimir N. Uversky
New Technologies To Analyse Protein Function: An Intrinsic Disorder Perspective, Vladimir N. Uversky
Molecular Medicine Faculty Publications
Functions of intrinsically disordered proteins do not require structure. Such structure-independent functionality has melted away the classic rigid “lock and key” representation of structure–function relationships in proteins, opening a new page in protein science, where molten keys operate on melted locks and where conformational flexibility and intrinsic disorder, structural plasticity and extreme malleability, multifunctionality and binding promiscuity represent a new-fangled reality. Analysis and understanding of this new reality require novel tools, and some of the techniques elaborated for the examination of intrinsically disordered protein functions are outlined in this review.