Interface Structure and Dynamics in Polymer‐Nanoparticle Hybrids: A Review on Molecular Mechanisms Underlying the Improved Interfaces

2021 ◽  
Vol 6 (20) ◽  
pp. 5068-5096
Author(s):  
Mohammad Abdul Sattar
Keyword(s):  
Molecular Mechanisms ◽  
Interface Structure ◽  
Polymer Nanoparticle ◽  
Structure And Dynamics

scholarly journals Direct observation of structure and dynamics during phase separation of an elastomeric protein

2017 ◽  
Vol 114 (22) ◽  
pp. E4408-E4415 ◽  
Author(s):  
Sean E. Reichheld ◽  
Lisa D. Muiznieks ◽  
Fred W. Keeley ◽  
Simon Sharpe
Keyword(s):  
Phase Separation ◽  
Matrix Protein ◽  
Molecular Mechanisms ◽  
Bulk Water ◽  
Extracellular Matrix Protein ◽  
Elastic Fibers ◽  
Cross Linking ◽  
Structure And Dynamics ◽  
Chemical Cross Linking

Despite its growing importance in biology and in biomaterials development, liquid–liquid phase separation of proteins remains poorly understood. In particular, the molecular mechanisms underlying simple coacervation of proteins, such as the extracellular matrix protein elastin, have not been reported. Coacervation of the elastin monomer, tropoelastin, in response to heat and salt is a critical step in the assembly of elastic fibers in vivo, preceding chemical cross-linking. Elastin-like polypeptides (ELPs) derived from the tropoelastin sequence have been shown to undergo a similar phase separation, allowing formation of biomaterials that closely mimic the material properties of native elastin. We have used NMR spectroscopy to obtain site-specific structure and dynamics of a self-assembling elastin-like polypeptide along its entire self-assembly pathway, from monomer through coacervation and into a cross-linked elastic material. Our data reveal that elastin-like hydrophobic domains are composed of transient β-turns in a highly dynamic and disordered chain, and that this disorder is retained both after phase separation and in elastic materials. Cross-linking domains are also highly disordered in monomeric and coacervated ELP3 and form stable helices only after chemical cross-linking. Detailed structural analysis combined with dynamic measurements from NMR relaxation and diffusion data provides direct evidence for an entropy-driven mechanism of simple coacervation of a protein in which transient and nonspecific intermolecular hydrophobic contacts are formed by disordered chains, whereas bulk water and salt are excluded.

scholarly journals Flagella-Driven Motility of Bacteria

Biomolecules ◽  
2019 ◽  
Vol 9 (7) ◽  
pp. 279 ◽  
Author(s):  
Shuichi Nakamura ◽  
Tohru Minamino
Keyword(s):  
Cell Body ◽  
Molecular Mechanisms ◽  
Bacterial Species ◽  
Structural Diversity ◽  
Flagellar Motor ◽  
Bacterial Flagellum ◽  
Structure And Dynamics ◽  
Ring Complex ◽  
Flagellar Filament ◽  
Experimental And Theoretical Studies

The bacterial flagellum is a helical filamentous organelle responsible for motility. In bacterial species possessing flagella at the cell exterior, the long helical flagellar filament acts as a molecular screw to generate thrust. Meanwhile, the flagella of spirochetes reside within the periplasmic space and not only act as a cytoskeleton to determine the helicity of the cell body, but also rotate or undulate the helical cell body for propulsion. Despite structural diversity of the flagella among bacterial species, flagellated bacteria share a common rotary nanomachine, namely the flagellar motor, which is located at the base of the filament. The flagellar motor is composed of a rotor ring complex and multiple transmembrane stator units and converts the ion flux through an ion channel of each stator unit into the mechanical work required for motor rotation. Intracellular chemotactic signaling pathways regulate the direction of flagella-driven motility in response to changes in the environments, allowing bacteria to migrate towards more desirable environments for their survival. Recent experimental and theoretical studies have been deepening our understanding of the molecular mechanisms of the flagellar motor. In this review article, we describe the current understanding of the structure and dynamics of the bacterial flagellum.

scholarly journals Real-Time Observation of Structure and Dynamics during the Liquid-to-Solid Transition of FUS LC

2020 ◽  
Author(s):  
Raymond F. Berkeley ◽  
Maryam Kashefi ◽  
Galia T. Debelouchina
Keyword(s):  
Nmr Spectroscopy ◽  
Real Time ◽  
Molecular Mechanisms ◽  
Rna Binding ◽  
Cell Function ◽  
Magic Angle Spinning ◽  
Mas Nmr ◽  
Magic Angle ◽  
Structure And Dynamics ◽  
Liquid To Solid Transition

AbstractMany of the proteins found in pathological protein fibrils also exhibit tendencies for liquid-liquid phase separation (LLPS) both in vitro and in cells. The mechanisms underlying the connection between these phase transitions have been challenging to study due to the heterogeneous and dynamic nature of the states formed during the maturation of LLPS protein droplets into gels and solid aggregates. Here, we interrogate the liquid-to-solid transition of the low complexity domain of the RNA binding protein FUS (FUS LC), which has been shown to adopt LLPS, gel-like, and amyloid states. We employ magic-angle spinning (MAS) NMR spectroscopy which has allowed us to follow these transitions in real time and with residue specific resolution. We observe the development of β-sheet structure through the maturation process and show that the final state of FUS LC fibrils produced through LLPS is distinct from that grown from fibrillar seeds. We also apply our methodology to FUS LC G156E, a clinically relevant FUS mutant that exhibits accelerated fibrillization rates. We observe significant changes in dynamics during the transformation of the FUS LC G156E construct and begin to unravel the sequence specific contributions to this phenomenon with computational studies of the phase separated state of FUS LC and FUS LC G156E.SignificanceThe presence of protein aggregates and plaques in the brain is a common pathological sign of neurodegenerative disease. Recent work has revealed that many of the proteins found in these aggregates can also form liquid-liquid droplets and gels. While the interconversion from one state to another can have vast implications for cell function and disease, the molecular mechanisms that underlie these processes are not well understood. Here, we combine MAS NMR spectroscopy with other biophysical and computational tools to follow the transitions of the stress response protein FUS. This approach has allowed us to observe real-time changes in structure and dynamics as the protein undergoes these transitions, and to reveal the intricate effects of disease-relevant mutations on the transformation process.

scholarly journals 1H, 13C and 15N resonance assignment of the SARS-CoV-2 full-length nsp1 protein and its mutants reveals its unique secondary structure features in solution

PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0251834
Author(s):  
Tatiana Agback ◽  
Francisco Dominguez ◽  
Ilya Frolov ◽  
Elena I. Frolova ◽  
Peter Agback
Keyword(s):  
Secondary Structure ◽  
Molecular Mechanisms ◽  
Full Length ◽  
Intramolecular Interactions ◽  
Nmr Studies ◽  
Intrinsically Disordered ◽  
Structure And Dynamics ◽  
High Resolution Nmr ◽  
In The Beginning

Structural characterization of the SARS-CoV-2 full length nsp1 protein will be an essential tool for developing new target-directed antiviral drugs against SARS-CoV-2 and for further understanding of intra- and intermolecular interactions of this protein. As a first step in the NMR studies of the protein, we report the 1H, 13C and 15N resonance backbone assignment as well as the Cβ of the apo form of the full-lengthSARS-CoV-2 nsp1 including the folded domain together with the flaking N- and C- terminal intrinsically disordered fragments. The 19.8 kD protein was characterized by high-resolution NMR. Validation of assignment have been done by using two different mutants, H81P and K129E/D48E as well as by amino acid specific experiments. According to the obtained assignment, the secondary structure of the folded domain in solution was almost identical to its previously published X-ray structure as well as another published secondary structure obtained by NMR, but some discrepancies have been detected. In the solution SARS-CoV-2 nsp1 exhibited disordered, flexible N- and C-termini with different dynamic characteristics. The short peptide in the beginning of the disordered C-terminal domain adopted two different conformations distinguishable on the NMR time scale. We propose that the disordered and folded nsp1 domains are not fully independent units but are rather involved in intramolecular interactions. Studies of the structure and dynamics of the SARS-CoV-2 mutant in solution are on-going and will provide important insights into the molecular mechanisms underlying these interactions.

scholarly journals N6-methyladenosine binding induces a metal-centered rearrangement that activates the human RNA demethylase Alkbh5

2021 ◽  
Vol 7 (34) ◽  
pp. eabi8215
Author(s):  
Jeffrey A. Purslow ◽  
Trang T. Nguyen ◽  
Balabhadra Khatiwada ◽  
Aayushi Singh ◽  
Vincenzo Venditti
Keyword(s):  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Stem Cell Differentiation ◽  
Solution Nmr ◽  
Epigenetic Mark ◽  
Structure And Dynamics ◽  
Physiological Processes ◽  
Canonical Base ◽  
Control Gene Expression ◽  
Coupled Reactions

Alkbh5 catalyzes demethylation of the N6-methyladenosine (m6A), an epigenetic mark that controls several physiological processes including carcinogenesis and stem cell differentiation. The activity of Alkbh5 comprises two coupled reactions. The first reaction involves decarboxylation of α-ketoglutarate (αKG) and formation of a Fe4+═O species. This oxyferryl intermediate oxidizes the m6A to reestablish the canonical base. Despite coupling between the two reactions being required for the correct Alkbh5 functioning, the mechanisms linking dioxygen activation to m6A binding are not fully understood. Here, we use solution NMR to investigate the structure and dynamics of apo and holo Alkbh5. We show that binding of m6A to Alkbh5 induces a metal-centered rearrangement of αKG that increases the exposed area of the metal, making it available for binding O2. Our study reveals the molecular mechanisms underlying activation of Alkbh5, therefore opening new perspectives for the design of novel strategies to control gene expression and cancer progression.

scholarly journals A Survey of Computational Treatments of Biomolecules by Robotics-Inspired Methods Modeling Equilibrium Structure and Dynamic

2016 ◽  
Vol 57 ◽  
pp. 509-572 ◽  
Author(s):  
Amarda Shehu ◽  
Erion Plaku
Keyword(s):  
Molecular Mechanisms ◽  
Biological Function ◽  
Equilibrium Structure ◽  
Critical Discussion ◽  
Molecular Processes ◽  
Biomolecular Structure ◽  
Large Molecules ◽  
Physiological Conditions ◽  
Cellular Processes ◽  
Structure And Dynamics

More than fifty years of research in molecular biology have demonstrated that the ability of small and large molecules to interact with one another and propagate the cellular processes in the living cell lies in the ability of these molecules to assume and switch between specific structures under physiological conditions. Elucidating biomolecular structure and dynamics at equilibrium is therefore fundamental to furthering our understanding of biological function, molecular mechanisms in the cell, our own biology, disease, and disease treatments. By now, there is a wealth of methods designed to elucidate biomolecular structure and dynamics contributed from diverse scientific communities. In this survey, we focus on recent methods contributed from the Robotics community that promise to address outstanding challenges regarding the disparate length and time scales that characterize dynamic molecular processes in the cell. In particular, we survey robotics-inspired methods designed to obtain efficient representations of structure spaces of molecules in isolation or in assemblies for the purpose of characterizing equilibrium structure and dynamics. While an exhaustive review is an impossible endeavor, this survey balances the description of important algorithmic contributions with a critical discussion of outstanding computational challenges. The objective is to spur further research to address outstanding challenges in modeling equilibrium biomolecular structure and dynamics.

Hierarchical Structure and Dynamics of a Polymer/Nanoparticle Hybrid Displaying Attractive Polymer–Particle Interaction

2019 ◽  
Vol 52 (22) ◽  
pp. 8741-8750
Author(s):  
Bradley W. Mansel ◽  
Chun-Yu Chen ◽  
Jhih-Min Lin ◽  
Yu-Shan Huang ◽  
Yu-Chiao Lin ◽  
...  
Keyword(s):  
Hierarchical Structure ◽  
Particle Interaction ◽  
Polymer Particle ◽  
Polymer Nanoparticle ◽  
Structure And Dynamics
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