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Protein Science : a Publication of the... Jun 2020Several cellular processes rely on a cohort of dedicated proteins that manage tubulation, fission, and fusion of membranes. A notably large number of them belong to the... (Review)
Review
Several cellular processes rely on a cohort of dedicated proteins that manage tubulation, fission, and fusion of membranes. A notably large number of them belong to the dynamin superfamily of proteins. Among them is the evolutionarily conserved group of ATP-binding Eps15-homology domain-containing proteins (EHDs). In the two decades since their discovery, EHDs have been linked to a range of cellular processes that require remodeling or maintenance of specific membrane shapes such as during endocytic recycling, caveolar biogenesis, ciliogenesis, formation of T-tubules in skeletal muscles, and membrane resealing after rupture. Recent work has shed light on their structure and the unique attributes they possess in linking ATP hydrolysis to membrane remodeling. This review summarizes some of these recent developments and reconciles intrinsic protein functions to their cellular roles.
Topics: Adenosine Triphosphate; Animals; Humans; Hydrolysis; Protein Domains; Vesicular Transport Proteins
PubMed: 32223019
DOI: 10.1002/pro.3860 -
The Journal of Physical Chemistry... Nov 2023The present work combines the near edge X-ray absorption mass spectrometry of a protonated adenosine 5'-triphosphate (ATP) molecule isolated in an ion trap with...
The present work combines the near edge X-ray absorption mass spectrometry of a protonated adenosine 5'-triphosphate (ATP) molecule isolated in an ion trap with (time-dependent) density functional theory calculations. Our study unravels the effect of protonation on the ATP structure and its spectral properties, providing structure-property relationships at atomistic resolution for protonated ATP (ATPH) isolated in the gas-phase conditions. On the other hand, the present C and N K-edge X-ray absorption spectra of isolated ATPH appear closely like those previously reported for solvated ATP at low pH. Therefore, the present work should be relevant for further investigation and modeling of structure-function properties of protonated adenine and ATP in complex biological environments.
Topics: Molecular Structure; X-Rays; Adenosine Triphosphate; Adenosine
PubMed: 37925744
DOI: 10.1021/acs.jpclett.3c01666 -
Scientific Reports Feb 2019Synthesis of ATP by the FF ATP synthase in mitochondria and most bacteria is energized by the proton motive force (pmf) established and maintained by respiratory chain...
Synthesis of ATP by the FF ATP synthase in mitochondria and most bacteria is energized by the proton motive force (pmf) established and maintained by respiratory chain enzymes. Conversely, in the presence of ATP and in the absence of a pmf, the enzyme works as an ATP-driven proton pump. Here, we investigate how high concentrations of ATP affect the enzymatic activity of the FF ATP synthase under high pmf conditions, which is the typical situation in mitochondria or growing bacteria. Using the ATP analogue adenosine 5'-O-(1-thiotriphosphate) (ATPαS), we have developed a modified luminescence-based assay to measure ATP synthesis in the presence of millimolar ATP concentrations, replacing an assay using radioactive nucleotides. In inverted membrane vesicles of E. coli, we found that under saturating pmf conditions, ATP synthesis was reduced to ~10% at 5 mM ATPαS. This reduction was reversed by ADP, but not P, indicating that the ATP/ADP ratio controls the ATP synthesis rate. Our data suggests that the ATP/ADP ratio ~30 in growing E. coli limits the ATP synthesis rate to ~20% of the maximal rate possible at the applied pmf and that the rate reduction occurs via product inhibition rather than an increased ATP hydrolysis rate.
Topics: Adenosine Diphosphate; Adenosine Triphosphate; Escherichia coli; Hydrolysis; Luminescent Measurements
PubMed: 30816129
DOI: 10.1038/s41598-019-38564-0 -
Current Drug Targets Aug 2008Protein kinase C (PKC) is a family of kinases that plays diverse roles in many cellular functions, notably proliferation, differentiation, and cell survival. PKC is... (Review)
Review
Protein kinase C (PKC) is a family of kinases that plays diverse roles in many cellular functions, notably proliferation, differentiation, and cell survival. PKC is processed by phosphorylation and regulated by cofactor binding and subcellular localization. Extensive detail is available on the molecular mechanisms that regulate the maturation, activation, and signaling of PKC. However, less information is available on how signaling is terminated both from a global perspective and isozyme-specific differences. To target PKC therapeutically, various ATP-competitive inhibitors have been developed, but this method has problems with specificity. One possible new approach to developing novel, specific therapeutics for PKC would be to target the signaling termination pathways of the enzyme. This review focuses on the new developments in understanding how PKC signaling is terminated and how current drug therapies as well as information obtained from the recent elucidation of various PKC structures and down-regulation pathways could be used to develop novel and specific therapeutics for PKC.
Topics: Adenosine Triphosphate; Animals; Down-Regulation; Drug Delivery Systems; Humans; Protein Kinase C; Signal Transduction
PubMed: 18691009
DOI: 10.2174/138945008785132411 -
Protein Science : a Publication of the... Feb 2020Translocases of the AAA+ (ATPases Associated with various cellular Activities) family are powerful molecular machines that use the mechano-chemical coupling of ATP... (Review)
Review
Translocases of the AAA+ (ATPases Associated with various cellular Activities) family are powerful molecular machines that use the mechano-chemical coupling of ATP hydrolysis and conformational changes to thread DNA or protein substrates through their central channel for many important biological processes. These motors comprise hexameric rings of ATPase subunits, in which highly conserved nucleotide-binding domains form active-site pockets near the subunit interfaces and aromatic pore-loop residues extend into the central channel for substrate binding and mechanical pulling. Over the past 2 years, 41 cryo-EM structures have been solved for substrate-bound AAA+ translocases that revealed spiral-staircase arrangements of pore-loop residues surrounding substrate polypeptides and indicating a conserved hand-over-hand mechanism for translocation. The subunits' vertical positions within the spiral arrangements appear to be correlated with their nucleotide states, progressing from ATP-bound at the top to ADP or apo states at the bottom. Studies describing multiple conformations for a particular motor illustrate the potential coupling between ATP-hydrolysis steps and subunit movements to propel the substrate. Experiments with double-ring, Type II AAA+ motors revealed an offset of hydrolysis steps between the two ATPase domains of individual subunits, and the upper ATPase domains lacking aromatic pore loops frequently form planar rings. This review summarizes the critical advances provided by recent studies to our structural and functional understanding of hexameric AAA+ translocases, as well as the important outstanding questions regarding the underlying mechanisms for coordinated ATP-hydrolysis and mechano-chemical coupling.
Topics: Adenosine Triphosphatases; Adenosine Triphosphate; Humans; Hydrolysis; Models, Molecular; Molecular Conformation
PubMed: 31599052
DOI: 10.1002/pro.3743 -
PLoS Computational Biology Sep 2014Adenosine-5'-triphosphate (ATP) is generally regarded as a substrate for energy currency and protein modification. Recent findings uncovered the allosteric function of...
Adenosine-5'-triphosphate (ATP) is generally regarded as a substrate for energy currency and protein modification. Recent findings uncovered the allosteric function of ATP in cellular signal transduction but little is understood about this critical behavior of ATP. Through extensive analysis of ATP in solution and proteins, we found that the free ATP can exist in the compact and extended conformations in solution, and the two different conformational characteristics may be responsible for ATP to exert distinct biological functions: ATP molecules adopt both compact and extended conformations in the allosteric binding sites but conserve extended conformations in the substrate binding sites. Nudged elastic band simulations unveiled the distinct dynamic processes of ATP binding to the corresponding allosteric and substrate binding sites of uridine monophosphate kinase, and suggested that in solution ATP preferentially binds to the substrate binding sites of proteins. When the ATP molecules occupy the allosteric binding sites, the allosteric trigger from ATP to fuel allosteric communication between allosteric and functional sites is stemmed mainly from the triphosphate part of ATP, with a small number from the adenine part of ATP. Taken together, our results provide overall understanding of ATP allosteric functions responsible for regulation in biological systems.
Topics: Adenosine Triphosphate; Allosteric Site; Bacteria; Enzymes; Fungi; Humans; Molecular Dynamics Simulation; Proteins; Signal Transduction; Thermodynamics
PubMed: 25211773
DOI: 10.1371/journal.pcbi.1003831 -
Cell Mar 2017Modern metabolism would not work without ATP and phosphate, but in primordial biochemical networks, energy currencies might have been simpler. Goldford et al. report a...
Modern metabolism would not work without ATP and phosphate, but in primordial biochemical networks, energy currencies might have been simpler. Goldford et al. report a novel systems approach to reconstructing energetics in ancient metabolism, with very interesting results.
Topics: Adenosine Triphosphate; Energy Metabolism
PubMed: 28283068
DOI: 10.1016/j.cell.2017.02.032 -
Current Biology : CB Jan 2004
Topics: Adenosine Triphosphate; Cations; Ion Channels; Signal Transduction
PubMed: 14711422
DOI: 10.1016/j.cub.2003.12.009 -
Experimental Physiology Jun 2019
Topics: Adenosine Triphosphate; Animals; Humans
PubMed: 31148324
DOI: 10.1113/EP087583 -
British Journal of Pharmacology Jan 19791 High concentrations of adenosine 5'-triphosphate (ATP, 100 to 1000 micrometer) were required to cause contraction of the rat urinary bladder, while adenosine and...
1 High concentrations of adenosine 5'-triphosphate (ATP, 100 to 1000 micrometer) were required to cause contraction of the rat urinary bladder, while adenosine and adenosine 5'monophosphate (AMP, 1 to 50 micrometer) produced relaxation. 2 One hundred fold lower concentrations of beta-gamma-methylene ATP, which is resistant to degradation to AMP and adenosine, caused dose-dependent, phasic contractions which mimicked atropine-resistant responses to nerve stimulation. 3 Adenosine and AMP caused dose-dependent inhibition of carbachol-induced contractions; theophylline competitively antagonized this inhibition but not the contractile responses to beta-gamma-methylene ATP, ATP or atropine-resistant nerve stimulation. 4 These results suggest that the insensitivity of the rat bladder to ATP is due to its rapid degradation to AMP and adenosine and support the hypothesis that the bladder receives a purinergic excitatory innervation.
Topics: Adenosine; Adenosine Monophosphate; Adenosine Triphosphate; Animals; Electric Stimulation; In Vitro Techniques; Male; Muscle Contraction; Muscle, Smooth; Rats; Urinary Bladder
PubMed: 760894
DOI: 10.1111/j.1476-5381.1979.tb17337.x