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Full-Text Articles in Medicine and Health Sciences
Pre-Molten, Wet, And Dry Molten Globules En Route To The Functional State Of Proteins, Munishwar Nath Gupta, Vladimir N. Uversky
Pre-Molten, Wet, And Dry Molten Globules En Route To The Functional State Of Proteins, Munishwar Nath Gupta, Vladimir N. Uversky
Molecular Medicine Faculty Publications
Transitions between the unfolded and native states of the ordered globular proteins are accompanied by the accumulation of several intermediates, such as pre-molten globules, wet molten globules, and dry molten globules. Structurally equivalent conformations can serve as native functional states of intrinsically disordered proteins. This overview captures the characteristics and importance of these molten globules in both structured and intrinsically disordered proteins. It also discusses examples of engineered molten globules. The formation of these intermediates under conditions of macromolecular crowding and their interactions with nanomaterials are also reviewed.
Arrow Of Time, Entropy, And Protein Folding: Holistic View On Biochirality, Victor V. Dyakin, Vladimir N. Uversky
Arrow Of Time, Entropy, And Protein Folding: Holistic View On Biochirality, Victor V. Dyakin, Vladimir N. Uversky
Molecular Medicine Faculty Publications
Chirality is a universal phenomenon, embracing the space–time domains of non-organic and organic nature. The biological time arrow, evident in the aging of proteins and organisms, should be linked to the prevalent biomolecular chirality. This hypothesis drives our exploration of protein aging, in relation to the biological aging of an organism. Recent advances in the chirality discrimination methods and theoretical considerations of the non-equilibrium thermodynamics clarify the fundamental issues, concerning the biphasic, alternative, and stepwise changes in the conformational entropy associated with protein folding. Living cells represent open, non-equilibrium, self-organizing, and dissipative systems. The non-equilibrium thermodynamics of cell biology are …
The Finite Size Effects And Two-State Paradigm Of Protein Folding, Artem Badasyan, Matjaz Valant, Jože Grdadolnik, Vladimir N. Uversky
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 …
Life In Phases: Intra- And Inter- Molecular Phase Transitions In Protein Solutions, Vladimir N. Uversky, Alexey V. Finkelstein
Life In Phases: Intra- And Inter- Molecular Phase Transitions In Protein Solutions, Vladimir N. Uversky, Alexey V. Finkelstein
Molecular Medicine Faculty Publications
Proteins, these evolutionarily-edited biological polymers, are able to undergo intramolecular and intermolecular phase transitions. Spontaneous intramolecular phase transitions define the folding of globular proteins, whereas binding-induced, intra- and inter- molecular phase transitions play a crucial role in the functionality of many intrinsically-disordered proteins. On the other hand, intermolecular phase transitions are the behind-the-scenes players in a diverse set of macrosystemic phenomena taking place in protein solutions, such as new phase nucleation in bulk, on the interface, and on the impurities, protein crystallization, protein aggregation, the formation of amyloid fibrils, and intermolecular liquid–liquid or liquid–gel phase transitions associated with the biogenesis …
Structure And Conformational Properties Of D-Glucose/D-Galactose-Binding Protein In Crowded Milieu, Alexander V. Fonin, Sergey A. Silonov, Asiia K. Sitdikova, Irina M. Kuznetsova, Vladimir N. Uversky
Structure And Conformational Properties Of D-Glucose/D-Galactose-Binding Protein In Crowded Milieu, Alexander V. Fonin, Sergey A. Silonov, Asiia K. Sitdikova, Irina M. Kuznetsova, Vladimir N. Uversky
Molecular Medicine Faculty Publications
Conformational changes of d-glucose/d-galactose-binding protein (GGBP) were studied under molecular crowding conditions modeled by concentrated solutions of polyethylene glycols (PEG-12000, PEG-4000, and PEG-600), Ficoll-70, and Dextran-70, addition of which induced noticeable structural changes in the GGBP molecule. All PEGs promoted compaction of GGBP and lead to the increase in ordering of its structure. Concentrated solutions of PEG-12000 and PEG-4000 caused GGBP aggregation. Although Ficoll-70 and Dextran-70 also promoted increase in the GGBP ordering, the structural outputs were different for different crowders. For example, in comparison with the GGBP in buffer, the intrinsic fluorescence spectrum of this protein was shifted to …
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
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 …
Extracting Structural Information From Charge-State Distributions Of Intrinsically Disordered Proteins By Non-Denaturing Electrospray-Ionization Mass Spectrometry, Lorenzo Testa, Stefania Brocca, Carlo Santambrogio, Annalisa D'Urzo, Johnny Habchi, Sonia Longhi, Vladimir N. Uversky, Rita Grandori
Extracting Structural Information From Charge-State Distributions Of Intrinsically Disordered Proteins By Non-Denaturing Electrospray-Ionization Mass Spectrometry, Lorenzo Testa, Stefania Brocca, Carlo Santambrogio, Annalisa D'Urzo, Johnny Habchi, Sonia Longhi, Vladimir N. Uversky, Rita Grandori
Molecular Medicine Faculty Publications
Intrinsically disordered proteins (IDPs) exert key biological functions but tend to escape identification and characterization due to their high structural dynamics and heterogeneity. The possibility to dissect conformational ensembles by electrospray-ionization mass spectrometry (ESI-MS) offers an attracting possibility to develop a signature for this class of proteins based on their peculiar ionization behavior. This review summarizes available data on charge-state distributions (CSDs) obtained for IDPs by non-denaturing ESI-MS, with reference to globular or chemically denatured proteins. The results illustrate the contributions that direct ESI-MS analysis can give to the identification of new putative IDPs and to their conformational investigation.
Influence Of Sequence Changes And Environment On Intrinsically Disordered Proteins, Amrita Mohan, Vladimir N. Uversky, Predrag Radivojac
Influence Of Sequence Changes And Environment On Intrinsically Disordered Proteins, Amrita Mohan, Vladimir N. Uversky, Predrag Radivojac
Molecular Medicine Faculty Publications
Many large-scale studies on intrinsically disordered proteins are implicitly based on the structural models deposited in the Protein Data Bank. Yet, the static nature of deposited models supplies little insight into variation of protein structure and function under diverse cellular and environmental conditions. While the computational predictability of disordered regions provides practical evidence that disorder is an intrinsic property of proteins, the robustness of disordered regions to changes in sequence or environmental conditions has not been systematically studied. We analyzed intrinsically disordered regions in the same or similar proteins crystallized independently and studied their sensitivity to changes in protein sequence …