scholarly journals Revisiting the protomotive vectorial motion of F0-ATPase

2019 ◽  
Vol 116 (39) ◽  
pp. 19484-19489 ◽  
Author(s):  
Chen Bai ◽  
Arieh Warshel
Keyword(s):  
Proton Transport ◽  
Structural Model ◽  
Water Flooding ◽  
Coarse Grained ◽  
Subunit C ◽  
Detailed Mechanism ◽  
Actual Mechanism ◽  
Atpase System ◽  
Transport Path ◽  
Electrostatic Coupling

The elucidation of the detailed mechanism used by F0 to convert proton gradient to torque and rotational motion presents a major puzzle despite significant biophysical and structural progress. Although the conceptual model has advanced our understanding of the working principles of such systems, it is crucial to explore the actual mechanism using structure-based models that actually reproduce a unidirectional proton-driven rotation. Our previous work used a coarse-grained (CG) model to simulate the action of F0. However, the simulations were based on a very tentative structural model of the interaction between subunit a and subunit c. Here, we again use a CG model but with a recent cryo-EM structure of cF1F0 and also explore the proton path using our water flooding and protein dipole Langevin dipole semimacroscopic formalism with its linear response approximation version (PDLD/S-LRA) approaches. The simulations are done in the combined space defined by the rotational coordinate and the proton transport coordinate. The study reproduced the effect of the protomotive force on the rotation of the F0 while establishing the electrostatic origin of this effect. Our landscape reproduces the correct unidirectionality of the synthetic direction of the F0 rotation and shows that it reflects the combined electrostatic coupling between the proton transport path and the c-ring conformational change. This work provides guidance for further studies in other proton-driven mechanochemical systems and should lead (when combined with studies of F1) to a complete energy transduction picture of the F0F1-ATPase system.

DISTRIBUTION OF OIL FROM THE GULF WAR SPILL WITHIN INTERTIDAL HABITATS—ONE YEAR LATER

1993 ◽  
Vol 1993 (1) ◽  
pp. 373-381 ◽  
Author(s):  
Miles O. Hayes ◽  
Jacqueline Michel ◽  
Todd M. Montello ◽  
Ahmed M. Al-Mansi ◽  
John R. Jensen ◽  
...  
Keyword(s):  
Asphalt Pavement ◽  
Gulf War ◽  
Water Flooding ◽  
Coarse Grained ◽  
Tidal Range ◽  
Sediment Surface ◽  
Deep Penetration ◽  
High Porosity ◽  
Intertidal Sand ◽  
One Year

ABSTRACT Results of a land-based intertidal survey of the impacts of the Gulf War oil spill on the Saudi Arabian coast, carried out from 1 March to 4 April 1992 in conjunction with Leg II of the NOAA ship Mt. Mitchell's ROPME Sea cruise, show that there is a striking correlation between the nearshore geomorphology and the persistence of intertidal oil. Significant quantities of oil (measured in millions of gallons) remained in the sediments of the sheltered tidal flat/marsh areas, and significant erosion of oiled sediments has occurred along many of the outer exposed areas. A massive asphalt pavement, tens of meters wide and over 20 kilometers long, which is believed to have formed as a result of the Nowruz spill of 1983, occurs along the outer coast of the Abu Ali headland. Along certain other exposed outer sand beaches, conditions are conducive to the formation and preservation of a similar asphalt pavement as a result of the Gulf War spill. The most severely impacted areas studied were several halophyte marsh/algal mat complexes and mudflats at the heads of sheltered bays, where all the halophytes were dead and there was no sign of living epibiota in the mid to upper intertidal areas. Before the spill, burrowing infauna, such as crabs and polychaetes, occurred in large numbers in these sheltered areas. The previously occupied burrows were heavily oiled, with some containing liquid black oil to depths of over 40 cm. The deep penetration of oil into the burrows and probable slow weathering rates of the oil could result in many years of pollution of these sheltered habitats. The development of “bubble sand,” a sponge-like sand deposit with porosities probably as high as ± 50 percent, is a common phenomenon in the sheltered coarse-grained beaches and intertidal sand flats of the bays, covering hundreds of acres of intertidal area. The high porosity results from entrapment of air between the water table, which is lowered during low tide, and water flooding the sediment surface during rising tides. Depths of penetration of the oil into bubble sand exceeding 40 cm were found at several localities. This deep oil will also remain in the sediment for many years, because of the slow erosion rates that occur in these sheltered environments. In most places, the oiling extended all the way to the low-tide line (the tidal range is 0.5 to 1.5 m), but, one year later, the oil in the lower intertidal areas was generally restricted to the tops of intertidal sand bars. Many of the unoiled topographic lows between the bars and other unoiled portions of the lower flats were rich in epifaunal and infaunal populations of invertebrates and plants. Shorebirds were observed feeding in these unoiled areas.

scholarly journals Multiple interactions between an Arf/GEF complex and charged lipids determine activation kinetics on the membrane

2017 ◽  
Vol 114 (43) ◽  
pp. 11416-11421 ◽  
Author(s):  
Deepti Karandur ◽  
Agata Nawrotek ◽  
John Kuriyan ◽  
Jacqueline Cherfils
Keyword(s):  
Lipid Bilayer ◽  
Membrane Trafficking ◽  
Structural Model ◽  
High Efficiency ◽  
Structural Data ◽  
Lipid Binding ◽  
Small Gtpases ◽  
Coarse Grained ◽  
Nucleotide Exchange ◽  
Ph Domain

Lipidated small GTPases and their regulators need to bind to membranes to propagate actions in the cell, but an integrated understanding of how the lipid bilayer exerts its effect has remained elusive. Here we focused on ADP ribosylation factor (Arf) GTPases, which orchestrate a variety of regulatory functions in lipid and membrane trafficking, and their activation by the guanine-nucleotide exchange factor (GEF) Brag2, which controls integrin endocytosis and cell adhesion and is impaired in cancer and developmental diseases. Biochemical and structural data are available that showed the exceptional efficiency of Arf activation by Brag2 on membranes. We determined the high-resolution crystal structure of unbound Brag2 containing the GEF (Sec7) and membrane-binding (pleckstrin homology) domains, revealing that it has a constitutively active conformation. We used this structure to analyze the interaction of uncomplexed Brag2 and of the myristoylated Arf1/Brag2 complex with a phosphatidylinositol bisphosphate (PIP2) -containing lipid bilayer, using coarse-grained molecular dynamics. These simulations revealed that the system forms a close-packed, oriented interaction with the membrane, in which multiple PIP2 lipids bind the canonical lipid-binding site and unique peripheral sites of the PH domain, the Arf GTPase and, unexpectedly, the Sec7 domain. We cross-validated these predictions by reconstituting the binding and kinetics of Arf and Brag2 in artificial membranes. Our coarse-grained structural model thus suggests that the high efficiency of Brag2 requires interaction with multiple lipids and a well-defined orientation on the membrane, resulting in a local PIP2 enrichment, which has the potential to signal toward the Arf pathway.

scholarly journals Mechanistic basis for motor-driven membrane constriction by dynamin

2020 ◽  
Author(s):  
Oleg Ganichkin ◽  
Renee Vancraenenbroeck ◽  
Gabriel Rosenblum ◽  
Hagen Hofmann ◽  
Alexander S. Mikhailov ◽  
...  
Keyword(s):  
Single Molecule ◽  
Structural Model ◽  
Molecular Motor ◽  
Coarse Grained ◽  
Gtp Hydrolysis ◽  
Single Molecule Fret ◽  
Membrane Tube ◽  
Mechanistic Basis ◽  
Dynamics Simulations ◽  
Gtpase Cycle

AbstractThe mechano-chemical GTPase dynamin assembles on membrane necks of clathrin-coated vesicles into helical oligomers that constrict and eventually cleave the necks in a GTP-dependent way. It remains not clear whether dynamin achieves this via molecular motor activity and, if so, by what mechanism. Here, we used ensemble kinetics, single-molecule FRET and molecular dynamics simulations to characterize dynamin’s GTPase cycle and determine the powerstroke strength. The results were incorporated into a coarse-grained structural model of dynamin filaments on realistic membrane templates. Working asynchronously, dynamin’s motor modules were found to collectively constrict a membrane tube. Force is generated by motor dimers linking adjacent helical turns and constriction is accelerated by their strain-dependent dissociation. Consistent with experiments, less than a second is needed to constrict a membrane tube to the hemi-fission radius. Thus, a membrane remodeling mechanism relying on cooperation of molecular ratchet motors driven by GTP hydrolysis has been revealed.

Coarse-grained model of nanoscale segregation, water diffusion, and proton transport in Nafion membranes

2018 ◽  
Vol 148 (2) ◽  
pp. 024108 ◽  
Author(s):  
Aleksey Vishnyakov ◽  
Runfang Mao ◽  
Ming-Tsung Lee ◽  
Alexander V. Neimark
Keyword(s):  
Proton Transport ◽  
Water Diffusion ◽  
Coarse Grained ◽  
Coarse Grained Model ◽  
Nafion Membranes

scholarly journals A bacterial size law revealed by a coarse-grained model of cell physiology

2016 ◽  
Author(s):  
François Bertaux ◽  
Julius von Kügelgen ◽  
Samuel Marguerat ◽  
Vahid Shahrezaei
Keyword(s):  
Growth Rate ◽  
Cell Size ◽  
Mass Fraction ◽  
Structural Model ◽  
Experimental Studies ◽  
Coarse Grained ◽  
Cell Physiology ◽  
Bacterial Physiology ◽  
Coarse Grained Model ◽  
Growth Laws

AbstractUniversal observations in Biology are sometimes described as “laws”. InE. coli, experimental studies performed over the past six decades have revealed major growth laws relating ribosomal mass fraction and cell size to the growth rate. Because they formalize complex emerging principles in biology, growth laws have been instrumental in shaping our understanding of bacterial physiology. Here, we discovered a novel size law that connects cell size to the inverse of the metabolic proteome mass fraction and the active fraction of ribosomes. We used a simple whole-cell coarse-grained model of cell physiology that combines the proteome allocation theory and the structural model of cell division. The model captures all available experimental data connecting the cell proteome composition, ribosome activity, division size and growth rate in response to nutrient quality, antibiotic treatment and increased protein burden. Finally, a stochastic extension of the model explains non-trivial correlations observed in single cell experiments including the adder principle. This work provides a simple and robust theoretical framework for studying the fundamental principles of cell size determination in unicellular organisms.

scholarly journals Molecular mechanism of fusion pore formation driven by the neuronal SNARE complex

2018 ◽  
Vol 115 (50) ◽  
pp. 12751-12756 ◽  
Author(s):  
Satyan Sharma ◽  
Manfred Lindau
Keyword(s):  
Pore Formation ◽  
Structural Model ◽  
Snare Complex ◽  
Coarse Grained ◽  
Fusion Pore ◽  
Protein Mutants ◽  
Experimental Values ◽  
Dynamics Simulations ◽  
External Forces ◽  
Fusion Pores

Release of neurotransmitters from synaptic vesicles begins with a narrow fusion pore, the structure of which remains unresolved. To obtain a structural model of the fusion pore, we performed coarse-grained molecular dynamics simulations of fusion between a nanodisc and a planar bilayer bridged by four partially unzipped SNARE complexes. The simulations revealed that zipping of SNARE complexes pulls the polar C-terminal residues of the synaptobrevin 2 and syntaxin 1A transmembrane domains to form a hydrophilic core between the two distal leaflets, inducing fusion pore formation. The estimated conductances of these fusion pores are in good agreement with experimental values. Two SNARE protein mutants inhibiting fusion experimentally produced no fusion pore formation. In simulations in which the nanodisc was replaced by a 40-nm vesicle, an extended hemifusion diaphragm formed but a fusion pore did not, indicating that restricted SNARE mobility is required for rapid fusion pore formation. Accordingly, rapid fusion pore formation also occurred in the 40-nm vesicle system when SNARE mobility was restricted by external forces. Removal of the restriction is required for fusion pore expansion.

scholarly journals Mixing MARTINI: Electrostatic Coupling in Hybrid Atomistic–Coarse-Grained Biomolecular Simulations

2013 ◽  
Vol 117 (13) ◽  
pp. 3516-3530 ◽  
Author(s):  
Tsjerk A. Wassenaar ◽  
Helgi I. Ingólfsson ◽  
Marten Prieß ◽  
Siewert J. Marrink ◽  
Lars V. Schäfer
Keyword(s):  
Coarse Grained ◽  
Biomolecular Simulations ◽  
Electrostatic Coupling

scholarly journals Modeling Hsp70/Hsp40 interaction by multi-scale molecular simulations and coevolutionary sequence analysis

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Duccio Malinverni ◽  
Alfredo Jost Lopez ◽  
Paolo De Los Rios ◽  
Gerhard Hummer ◽  
Alessandro Barducci
Keyword(s):  
Sequence Analysis ◽  
Structural Model ◽  
Molecular Simulations ◽  
Binding Domain ◽  
Coarse Grained ◽  
Multi Scale ◽  
Atomistic Models ◽  
Evolutionarily Conserved ◽  
Structural Details ◽  
Shock Proteins

The interaction between the Heat Shock Proteins 70 and 40 is at the core of the ATPase regulation of the chaperone machinery that maintains protein homeostasis. However, the structural details of the interaction remain elusive and contrasting models have been proposed for the transient Hsp70/Hsp40 complexes. Here we combine molecular simulations based on both coarse-grained and atomistic models with coevolutionary sequence analysis to shed light on this problem by focusing on the bacterial DnaK/DnaJ system. The integration of these complementary approaches resulted in a novel structural model that rationalizes previous experimental observations. We identify an evolutionarily conserved interaction surface formed by helix II of the DnaJ J-domain and a structurally contiguous region of DnaK, involving lobe IIA of the nucleotide binding domain, the inter-domain linker, and the β-basket of the substrate binding domain.

The Reaction Mechanism of Phenylalanine Hydroxylase. – A Question of Coordination

Pteridines ◽  
2005 ◽  
Vol 16 (1) ◽  
pp. 27-34 ◽  
Author(s):  
Knut Teigen ◽  
Vidar R. Jensen ◽  
Aurora Martinez
Keyword(s):  
Density Functional ◽  
Structural Model ◽  
Phenylalanine Hydroxylase ◽  
Experimental Studies ◽  
Binding Mode ◽  
Heme Iron ◽  
Crystallographic Structure ◽  
Oxygen Binding ◽  
Non Heme Iron ◽  
Actual Mechanism

Abstract Phenylalanine hydroxylase (PAH) is a non-heme iron and tetrahydrobiopterin-dependent enzyme that catalyzes the hydroxylation of L-phenylalanine to L-tyrosine using dioxygen as additional substrate. The cofactor tetrahydrobiopterin accepts one of the oxygen atoms of dioxygen during catalysis and also seems to be involved in prereduction of the active site iron from the ferric to the activated ferrous form. Structures of the truncated form of PAH in complex with substrate and cofactor are available, but the oxygen binding site and the actual mechanism of electron transfer are uncertain. It is believed that dioxygen binds directly to the metal, where it is activated, and several reaction mechanisms involving end-on binding of 0 2 have been proposed based on both experimental studies and quantum mechanical calculations. However, in this work we aimed to investigate the possibility of side-on binding of dioxygen to the iron. Furthermore, NMR and recent high-resolution crystallographic studies also place the cofactor in closer proximity to the iron, challenging the mechanistic conclusions from earlier crystallographic and computational studies. In this paper we report preliminary results from a density functional theory (DFT) study of the coordination of dioxygen to a structural model of PAH based on a recent crystallographic structure. These results are compared with existing computational and experimental data and their implications for the mechanism of the PAH-reaction are discussed. Particular attention is paid to the binding-mode of dioxygen and the iron-cofactor distance.

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