Abstract:
:Deposition of misfolded alpha-synuclein is a critical factor in several neurodegenerative disorders. Filamentous alpha-synuclein is the major component of Lewy bodies and Lewy neurites, the intracellular inclusions in the dopaminergic neurons of the substantia nigra, which are considered the pathological hallmark of Parkinson's disease. We show here that anions induce partial folding of alpha-synuclein at neutral pH, forming a critical amyloidogenic intermediate, which leads to significant acceleration of the rate of fibrillation. The magnitude of the accelerating effect generally followed the position of the anions in the Hofmeister series, indicating a major role of protein-water-anion interactions in the process at salt concentrations above 10 mM. Below this concentration, electrostatic effects dominated in the mechanism of anion-induced fibrillation. The acceleration of fibrillation by anions was also dependent on the cation. Moderate concentrations of anions affected both the rates of nucleation and the elongation of alpha-synuclein fibrillation, primarily via their effect on the interaction of the protein with water.
journal_name
Biochemistryjournal_title
Biochemistryauthors
Munishkina LA,Henriques J,Uversky VN,Fink ALdoi
10.1021/bi034938rsubject
Has Abstractpub_date
2004-03-23 00:00:00pages
3289-300issue
11eissn
0006-2960issn
1520-4995journal_volume
43pub_type
杂志文章相关文献
BIOCHEMISTRY文献大全abstract::The leech carboxypeptidase inhibitor (LCI) is a 66-amino acid protein, containing four disulfides that stabilize its structure. This polypeptide represents an excellent model for the study and understanding of the diversity of folding pathways in small, cysteine-rich proteins. The pathway of oxidative folding of LCI h...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi034308p
更新日期:2003-06-10 00:00:00
abstract::Human serum albumin (HSA) is the most abundant protein in the blood plasma and is involved in the transport of metal ions. Four metal-binding sites with different specificities have been described in HSA: (i) the N-terminal site provided by Asp1, Ala2, and His3, (ii) the site at the reduced Cys34, (iii) site A, includ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi061783p
更新日期:2007-02-27 00:00:00
abstract::Mitochondria isolated from coenzyme Q deficient yeast cells had no detectable NADH:cytochrome c reductase or succinate:cytochrome c reductase but had comparable amounts of cytochromes b and c1 as wild-type mitochondria. Addition of succinate to the mutant mitochondria resulted in a slight reduction of cytochrome b; ho...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00372a029
更新日期:1986-12-02 00:00:00
abstract::DNA binding modes of distamycin (DST) were investigated via comparative binding studies with oligomeric duplexes of the form d(GCG-X-GCG).d(CGC-Y-CGC), where Y is complementary to X and X = 4- or 5-base binding site. It was found that 1:1 and 2:1 drug-duplex complexes exhibit distinctly different circular dichroic (CD...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi980950l
更新日期:1998-08-11 00:00:00
abstract::At neutral pH, compound I of Arthromyces ramosus peroxidase (ARP) was stable and was reduced to ferric ARP without apparent formation of compound II upon titration with ascorbate or hydroquinone. In the titration experiments, compound II was seen as an intermediate only at alkaline pH. However, measuring a difference ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00184a038
更新日期:1994-05-10 00:00:00
abstract::Transient contacts between denatured polypeptide chains are likely to play an important part in the initial stages of protein aggregation and fibrillation. To analyze the nature of such contacts, we have carried out a protein engineering study of the 102-residue protein U1A, which aggregates transiently in the wild-ty...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi048509k
更新日期:2004-10-19 00:00:00
abstract::A quartz-crystal microbalance (QCM) technique was applied to analyze effects of site-directed mutagenesis of a glycosidase (isomalto-dextranase) on the hydrolysis mechanism of the substrate binding (k(on), k(off), and K(d)) and the catalytic process (k(cat)), separately, by using a dextran-immobilized QCM in buffer so...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi050079q
更新日期:2005-07-12 00:00:00
abstract::The field of chemical site-selective modification of proteins has progressed extensively in recent decades to enable protein functionalization for imaging, drug delivery, and functional studies. In this Perspective, we provide detailed insight into an alternative use of site-selective protein chemistry to probe the ro...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/acs.biochem.8b00639
更新日期:2018-10-30 00:00:00
abstract::Applications of sensitive new technologies, in particular, two-dimensional NMR spectroscopy, have allowed detection of folded structures in short peptide fragments of proteins in aqueous solution under conditions where native proteins fold. These structures are in rapid dynamic exchange with unfolded states. These obs...
journal_title:Biochemistry
pub_type: 杂志文章,评审
doi:10.1021/bi00419a001
更新日期:1988-09-20 00:00:00
abstract::The transformation of DMPC vesicles containing myristic acid to larger structures was examined by nuclear magnetic resonance techniques. The process was found to be characterized by a rate which is approximately first order in vesicle concentration. Rates, however, show a dramatic increase with increasing myristic aci...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00610a027
更新日期:1978-08-22 00:00:00
abstract::Interactions of the beta subunit of the Oxytricha nova telomere binding protein with the telomeric DNA sequences, d(T4G4)2 and dT6(T4G4)2, have been investigated in vitro using Raman and fluorescence spectroscopies. Raman difference spectra show that the beta subunit binds to both d(T4G4)2 and dT6(T4G4)2 but promotes ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi972400d
更新日期:1998-02-03 00:00:00
abstract::The complete amino acid sequence of the major component myoglobin from Amazon River dolphin, Inia geoffrensis, was determined by specific cleavage of the protein to obtain large peptides which are readily degraded by the automatic sequencer. Three easily separable peptides were obtained by cleaving the protein with cy...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00695a018
更新日期:1975-12-02 00:00:00
abstract::Diverse voltage-gated K+ channels are produced by tetramerization of channel alpha subunits that can be encoded by multiple genes. In GH3 pituitary cells, the Kv1.4 and Kv1.5 subunit genes are constitutively expressed, and dexamethasone selectively up-regulates expression of the latter gene. Here we use subunit-specif...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi961290s
更新日期:1996-11-12 00:00:00
abstract::The cyclin-dependent kinase inhibitor p16(INK4a) (hereafter p16) functions as a multiple tumor suppressor. Mutations in p16, which are distributed throughout the entire protein, have been identified in a variety of human cancers and cancer-derived cell lines. It is unclear how tumor-derived mutations disrupt the struc...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi0117100
更新日期:2002-05-21 00:00:00
abstract::The protease prostate-specific antigen (PSA) is a marker widely used clinically for monitoring prostatic malignancies. Under normal conditions, this enzyme is mainly involved in the post ejaculation degradation of the major human seminal protein, the seminal plasma motility inhibitor precursor/semenogelin I (SPMIP/SgI...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi9626158
更新日期:1997-04-01 00:00:00
abstract::Reactivation of organophosphate (OP)-inhibited acetylcholinesterase (AChE) is a key objective in the treatment of OP poisoning. This study with native, wild-type, and mutant recombinant DNA-expressed AChEs, each inhibited by representative OP compounds, establishes a relationship between edrophonium acceleration of ox...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi9905720
更新日期:1999-08-03 00:00:00
abstract::The effect of calcium ion on the thermal stability of thermolysin has been investigated. The native protein undergoes an irreversible structural change and autolysis at high temperature. Analysis of the calcium ion dependence of the apparent melting temperature observed spectroscopically gives an apparent deltaH of -x...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00650a024
更新日期:1976-03-09 00:00:00
abstract::The pK(a) values measured previously for the internal Lys-66, Asp-66, and Glu-66 in variants of a highly stable form of staphylococcal nuclease are shifted by as many as 5 pK(a) units relative to normal pK(a) values in water. These shifts cannot be reproduced with continuum electrostatics calculations with static stru...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi902114m
更新日期:2010-05-18 00:00:00
abstract::Ribonuclease T1 was crystallized in the presence of vanadate(V). The crystal structure was solved by molecular replacement and refined by least-squares methods using stereochemical restraints. The refinement was based on data between 10 and 1.8 A and converged at a crystallographic R factor of 0.137. Except for the su...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00445a014
更新日期:1989-09-19 00:00:00
abstract::Thioredoxin reductase (TrxR) catalyzes the reduction of thioredoxin (Trx) by NADPH. A unique gene organization of TrxR and Trx has been found in Mycobacterium leprae, where TrxR and Trx are encoded by a single gene and, therefore, are expressed as a fusion protein (MlTrxR-Trx). This fusion enzyme is able to catalyze t...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi980754e
更新日期:1998-11-17 00:00:00
abstract::The aminoacylation kinetics of 19 different variants of yeast tRNATyr with nucleotide substitutions in positions 33-35 were determined. Substitution of the conserved uridine-33 does not alter the rate of aminoacylation. However, substitution of the anticodon position 34 or position 35 reduces Km from 2- to 10-fold and...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00367a072
更新日期:1986-09-23 00:00:00
abstract::Starting from a standard unfolded state (3.0 M guanidine hydrochloride, pH 7.2), the kinetics of refolding of iso-2-cytochrome c have been investigated as a function of final pH between pH 3 and pH 10. Absorbance in the ultraviolet and visible spectral regions and tryptophan fluorescence are used to monitor folding. O...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00419a020
更新日期:1988-09-20 00:00:00
abstract::A ribonuclease that hydrolyzes either linear duplex or single-stranded RNA in an exonucleolytic manner has been partially purified from Ehrlich ascites tumor cell nucleoli and is free from other ribonucleases. The enzyme will also degrade the RNA complement of an RNA X DNA duplex; however, no nuclease activity is obse...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00324a022
更新日期:1985-01-29 00:00:00
abstract::We report a new observation of the role of Escherichia coli single-strand DNA binding protein (SSB) in synthesis of primer RNA (pRNA) catalyzed by.E.coli primase on the SSB-coated phage G4oric template. Using a set of ATP priming substrates with reactive groups attached to the 5' gamma-phosphate on different length "a...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi972455f
更新日期:1998-03-17 00:00:00
abstract::A 15-residue fragment within the major continuous domain of gp120 from HIV-1 that can bind independently to the CD4 receptor has been shown to have the property of behaving as a solvent polarity-dependent conformational switch. The switch behavior (cooperative transition from beta-sheet to helical conformation as a fu...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi952045w
更新日期:1996-01-16 00:00:00
abstract::A molecular model has been built of the equine infectious anemia virus (EIAV) proteinase on the basis of the crystal structures of the related Rous sarcoma virus (RSV) and human immunodeficiency virus (HIV) proteinases. The 104 residue long EIAV proteinase has 30 identical and 11 similar amino acids compared to those ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00064a019
更新日期:1993-04-06 00:00:00
abstract::Methyl esterification of carboxylic acid residues in intact mouse S49 lymphoma cells was examined, and at least 24 proteins were found to be modified. Cell fractionation revealed that a distinct set of these proteins could be found in each of the four fractions. Nuclei contained 11 methyl-esterified proteins at 12, 15...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00344a053
更新日期:1985-11-05 00:00:00
abstract::The role of acidic amino acid residues in cation recognition and selectivity by the Na+/dicarboxylate cotransporter, NaDC-1, was investigated by site-directed mutagenesis and expression in Xenopus oocytes. Four of the residues tested, Asp-52, Glu-74, Glu-101, and Glu-332, were found to be unimportant for transport act...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi990076b
更新日期:1999-06-08 00:00:00
abstract::Design of a partially cysteine-depleted C98S/C239S/C377S/C468A cytochrome P450 3A4 mutant designated CYP3A4(C58,C64) allowed site-directed incorporation of thiol-reactive fluorescent probes into alpha-helix A. The site of modification was identified as Cys-64 with the help of CYP3A4(C58) and CYP3A4(C64), each bearing ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi061944p
更新日期:2007-01-09 00:00:00
abstract::The equilibrium binding and association kinetics of the Saccharomyces cerevisiae TATA Binding Protein (TBP) to the E4 and Major Late promoters of adenovirus (TATATATA and TATAAAAG, respectively), have been directly compared by quantitative DNase I titration and quench-flow "footprinting". The equilibrium binding of TB...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi981072u
更新日期:1998-11-10 00:00:00