Abstract:
:The plasma membrane of the cell is a complex, tightly regulated, heterogeneous environment shaped by proteins, lipids, and small molecules. Ca2+ ions are important cellular messengers, spatially separated from anionic lipids. After cell injury, disease, or apoptotic events, anionic lipids are externalized to the outer leaflet of the plasma membrane and encounter Ca2+, resulting in dramatic changes in the plasma membrane structure and initiation of signaling cascades. Despite the high chemical and biological significance, the structures of lipid-Ca2+ nanoclusters are still not known. Previously, we demonstrated by solid-state nuclear magnetic resonance (NMR) spectroscopy that upon binding to Ca2+, individual phosphatidylserine lipids populate two distinct yet-to-be-characterized structural environments. Here, we concurrently employ extensive all-atom molecular dynamics (MD) simulations with our accelerated membrane mimetic and detailed NMR measurements to identify lipid-Ca2+ nanocluster conformations. We find that major structural characteristics of these nanoclusters, including interlipid pair distances and chemical shifts, agree with observable NMR parameters. Simulations reveal that lipid-ion nanoclusters are shaped by two characteristic, long-lived lipid structures induced by divalent Ca2+. Using ab initio quantum mechanical calculations of chemical shifts on MD-captured lipid-ion complexes, we show that computationally observed conformations are validated by experimental NMR data. Both NMR measurements of diluted specifically labeled lipids and MD simulations reveal that the basic structural unit that reshapes the membrane is a Ca2+-coordinated phosphatidylserine tetramer. Our combined computational and experimental approach presented here can be applied to other complex systems in which charged membrane-active molecular agents leave structural signatures on lipids.
journal_name
Biochemistryjournal_title
Biochemistryauthors
Hallock MJ,Greenwood AI,Wang Y,Morrissey JH,Tajkhorshid E,Rienstra CM,Pogorelov TVdoi
10.1021/acs.biochem.8b01069subject
Has Abstractpub_date
2018-12-18 00:00:00pages
6897-6905issue
50eissn
0006-2960issn
1520-4995journal_volume
57pub_type
杂志文章相关文献
BIOCHEMISTRY文献大全abstract::The thermodynamics and kinetics of the subtransition L epsilon----P beta of sonicated unilamellar vesicles of 1-myristoyl-2-stearoylphosphatidylcholine (1M-2S-PC) and of 1-stearoyl-2-myristoylphosphatidylcholine (1S-2M-PC) were studied by equilibrium cooling curves and temperature-jump relaxation spectrometry with an ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00313a009
更新日期:1984-08-28 00:00:00
abstract::The inhibitory potency of 3'-azido-3'-deoxythymidine 5'-triphosphate (AZTTP) against HIV-1 reverse transcriptase (HIV-1 RT) has been further evaluated. The results indicate that the previously reported low Ki values for AZTTP against HIV-1 RT (2.35 nM) are due neither to the to the direct tight binding of AZTTP to HIV...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00120a013
更新日期:1992-02-11 00:00:00
abstract::Moesin binds to a large range of proteins through its N terminal FERM (band 4.1, ezrin, radixin, moesin) domain. In full-length moesin isolated from cells, this binding is masked by binding to the C-terminal domain of moesin (C-ERMAD). Activation takes place by phosphorylation of Thr 558 in the C-ERMAD, which releases...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi010419h
更新日期:2001-06-19 00:00:00
abstract::The complete primary structure of the major component myoglobin from the Arctic minke whale, Balaenoptera acutorostrata, was determined by specific cleavage of the protein to obtain large peptides which are readily degraded by the automatic sequencer. Over 80% of the amino acid sequence was established from the three ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00623a023
更新日期:1977-02-22 00:00:00
abstract::Proton and phosphorus-31 nuclear magnetic resonance (1H and 31P NMR) studies of the interaction between a tridecapeptide pheromone, the alpha-factor of Saccharomyces cerevisiae, and sonicated lipid vesicles are reported. 31P NMR studies demonstrate that there is interaction of the peptide with the phosphorus headgroup...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00436a017
更新日期:1989-05-16 00:00:00
abstract::Factor VIII (FVIII) is the nonproteolytic cofactor for FIXa in the tenase complex of blood coagulation. FVIII is proteolytically activated by thrombin and FXa in vitro to form a heterotrimer with full procoagulant activity. Activated protein C inactivates thrombin-activated FVIII through cleavage adjacent to position ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00125a022
更新日期:1992-03-17 00:00:00
abstract::The bidirectional transformation of a protein between its native water-soluble and integral transmembrane conformations is demonstrated for FraC, a hemolytic protein of the family of pore-forming toxins. In the presence of biological membranes, the water-soluble conformation of FraC undergoes a remarkable structural r...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/acs.biochem.5b01112
更新日期:2015-11-24 00:00:00
abstract::The unique characteristics of DNA charge transport (CT) have prompted an examination of roles for this chemistry within a biological context. Not only can DNA CT facilitate long-range oxidative damage of DNA, but redox-active proteins can couple to the DNA base stack and participate in long-range redox reactions using...
journal_title:Biochemistry
pub_type: 杂志文章,评审
doi:10.1021/bi501520w
更新日期:2015-02-03 00:00:00
abstract::UvrA is the ATPase subunit of the DNA repair enzyme (A)BC excinuclease. The amino acid sequence of this protein has revealed, in addition to two zinc fingers, three pairs of nucleotide binding motifs each consisting of a Walker A and B sequence. We have conducted site-specific mutagenesis, ATPase kinetic analyses, and...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00230a004
更新日期:1991-04-23 00:00:00
abstract::RosB catalyzes the formation of 8-aminoriboflavin 5'-phosphate (AFP), the key intermediate in roseoflavin biosynthesis, from the metabolic precursors riboflavin 5'-phosphate (RP, also known as FMN) and glutamate. The conversion of the aromatic methyl group at position 8 in RP into the aromatic amine in AFP occurs via ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/acs.biochem.8b00576
更新日期:2018-09-11 00:00:00
abstract::We have synthesized a series of N-propylamino-substituted benzazepinones (NPSBs) as specific probes for the benzothiazepinone (BTZ) binding domain of muscle L-type calcium channels (LTCCs). NPSBs were identified which possess high affinity for the channel after purification. We synthesized a fluorescent NPSB, DMBODIPY...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00010a039
更新日期:1995-03-14 00:00:00
abstract::Indolethylamine-N-methyltransferase (INMT) is a Class 1 transmethylation enzyme known for its production of N,N-dimethyltryptamine (DMT), a hallucinogen with affinity for various serotonergic, adrenergic, histaminergic, dopaminergic, and sigma-1 receptors. DMT is produced via the action of INMT on the endogenous subst...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi500175p
更新日期:2014-05-13 00:00:00
abstract::Lateral mobilities of fluorescent cell surface probes have been measured on normal (3T3) and transformed (SV3T3) cultured mouse fibroblasts. There is little discernible difference in the mobilities of a lipid analogue (diI), a fluorescent ganglioside derivative (GM1), and tetramethylrhodamine-labeled succinylated conc...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00551a011
更新日期:1980-05-13 00:00:00
abstract::In this paper, we examined the posttranslational modifications (PTMs) of high-mobility group A1 (HMGA1) proteins in PC-3 human prostate cancer cells that are either treated or not treated with a histone deacetylase inhibitor, sodium butyrate. We found that, from a reversed-phase C4 column, the HMGA1a protein eluted in...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi060504v
更新日期:2006-06-13 00:00:00
abstract::From the larger set of 191 variants at all the variable contact positions in the turkey ovomucoid third domain, we selected a subset that consists of Asp, Glu, His, and Lys residues at eight of the nine contiguous P6-P3' positions (residues 13-21), the exception being P3-Cys16 which is involved in a conserved disulfid...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi0269512
更新日期:2003-03-18 00:00:00
abstract::The solution structure of the complex formed between an oligodeoxynucleotide containing a two-base bulge (5'-CCATCGTCTACCTTTGGTAGGATGG) and SCA-alpha2, a designed spirocyclic helical molecule, has been elucidated. SCA-alpha2, a close mimic of the metabolite, NCSi-gb, of the DNA bulge-specific enediyne antibiotic neoca...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi602599d
更新日期:2007-04-24 00:00:00
abstract::AhpF, the flavoprotein reductase component of the Salmonella typhimurium alkyl hydroperoxide reductase system, catalyzes the reduction of an intersubunit disulfide bond in the peroxidatic active site of the system's other component, AhpC, a member of the peroxiredoxin family. Previous studies have shown that AhpF can ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi002766h
更新日期:2001-04-03 00:00:00
abstract::Reaction of 1-oxiranylpyrene (1-OP) with DNA and the structures of the covalent and noncovalent complexes formed were studied in aqueous media (5 mM phosphate buffer with 0.1 M NaCl, pH 7) by utilizing the techniques of absorption, fluorescence and linear dichroism spectroscopy in order to gain an understanding of pos...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00318a009
更新日期:1984-11-06 00:00:00
abstract::Evidence of nonequilibrium local heating in transient spectra of LHCII, the main light-harvesting complex of plants, was studied by using various excitation intensities over a wide temperature range, from 10 K to room temperature. No obvious manifestation of local heating was found at room temperature, whereas at 10 K...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi060048a
更新日期:2006-08-08 00:00:00
abstract::The mechanism of chromophore biosynthesis in green fluorescent protein (GFP) is triggered by a spontaneous main chain cyclization reaction of residues 65-67. Here, we demonstrate that the initially colorless Y66L variant, designed to trap chromophore precursor states, is oxidatively modified to generate yellow chromop...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi0503798
更新日期:2005-06-14 00:00:00
abstract::Yah1p, an [Fe 2S 2]-containing ferredoxin located in the matrix of Saccharomyces cerevisiae mitochondria, functions in the synthesis of Fe/S clusters and heme a prosthetic groups. EPR, Mossbauer spectroscopy, and electron microscopy were used to characterize the Fe that accumulates in Yah1p-depleted isolated intact mi...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi801047q
更新日期:2008-09-16 00:00:00
abstract::The structures of two RNA duplexes, whose sequences correspond to portions of the ColE1 plasmid copy control RNA I and RNA II, have been determined. Crystals containing the 18mers 5'-CA CCGUUGGUAGCGGUGC-3' and 5'-CACCGCUACCAACGGUGC-3' diffract to 1.20 A resolution while those containing the 19mers 5'-GCACCGUUGGUAGCGGU...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi9912793
更新日期:1999-11-09 00:00:00
abstract::Thermodynamic equilibrium transition models in DSC are only applicable to reversible processes, but reversibility of the thermal transitions of proteins is comparatively rare because of intermolecular aggregation of denatured proteins and the degradation that occurs at high temperatures. The cupredoxin azurin from Pse...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi0157621
更新日期:2002-01-22 00:00:00
abstract::Human cysteine-rich secretory protein 3 (CRISP-3; also known as SGP28) belongs to a family of closely related proteins found in mammals and reptiles. Some mammalian CRISPs are known to be involved in the process of reproduction, whereas some of the CRISPs from reptiles are neurotoxin-like substances found in lizard sa...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi048823e
更新日期:2004-10-12 00:00:00
abstract::Recent studies implicate hydrogen sulfide (H2S) oxidation as an important aspect of bacterial antibiotic resistance and sulfide homeostasis. The cst operon of the major human pathogen Staphylococcus aureus is induced by exogenous H2S stress and encodes enzymes involved in sulfide oxidation, including a group I flavopr...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/acs.biochem.6b00714
更新日期:2016-11-29 00:00:00
abstract::Compartmentation and NMR visibility of mitochondrial adenine nucleotides were quantitated in isolated rat liver mitochondria respiring on succinate and glutamate in vitro at 8 and 25 degrees C. Intra- and extramitochondrial nucleotides were discriminated by adding the chelator trans-1,2-diaminocyclohexane-N,N,N',N'-te...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00436a030
更新日期:1989-05-16 00:00:00
abstract::Atrazine chlorohydrolase (AtzA) from Pseudomonas sp. ADP initiates the metabolism of the herbicide atrazine by catalyzing a hydrolytic dechlorination reaction to produce hydroxyatrazine. Sequence analysis revealed AtzA to be homologous to metalloenzymes within the amidohydrolase protein superfamily. AtzA activity was ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi020415s
更新日期:2002-12-03 00:00:00
abstract::Modification of the bacterial cell wall heteropolymer peptidoglycan by addition of an acetyl group to the C-6 hydroxyl group of N-acetylmuramoyl residues is known to inhibit the activity of muramidases (lysozymes) of innate immune systems. The O-acetylation of peptidoglycan also precludes the action of intrinsic lytic...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi051679s
更新日期:2006-01-24 00:00:00
abstract::Spectrophotometric titration of pyridoxamine-pyruvate transaminase (EC 2.6.1.30) with pyridoxal at pH 7.15 gives four equivalent binding sites per tetramer. The pH dependence of the equilibrium constant for the association of 5'-deoxypyridoxal with the active site lysine residue was determined spectrophotometrically. ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00643a013
更新日期:1977-11-29 00:00:00
abstract::In the commonly used nucleation-dependent model of protein aggregation, aggregation proceeds only after a lag phase in which the concentration of energetically unfavorable nuclei reaches a critical value. The formation of oligomeric species prior to aggregation can be difficult to detect by current spectroscopic techn...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi400027y
更新日期:2013-03-19 00:00:00