Abstract:
:Amyloid diseases are caused by the self-assembly of a given protein into an insoluble cross-beta-sheet quaternary structural form which is pathogenic. An understanding of the biochemical mechanism of amyloid fibril formation should prove useful in understanding amyloid disease. Toward this end, a procedure for the conversion of the amyloidogenic protein transthyretin into amyloid fibrils under conditions which mimic the acidic environment of a lysosome has been developed. Association of a structured transthyretin denaturation intermediate is sufficient for amyloid fibril formation in vitro. The rate of fibril formation is pH dependent with significant rates being observed at pHs accessible within the lysosome (3.6-4.8). Far-UV CD spectroscopic studies suggest that transthyretin retains its secondary structural features at pHs where fibrils are formed. Near-UV CD studies demonstrate that transthyretin has retained the majority of its tertiary structure during fibril formation as well. Near-UV CD analysis in combination with glutaraldehyde cross-linking studies suggests that a pH-mediated tetramer to monomer transition is operative in the pH range where fibril formation occurs. The rate of fibril formation decreases markedly at pHs below pH 3.6, consistent with denaturation to a monomeric TTR intermediate which has lost its native tertiary structure and capability to form fibrils. It is difficult to specify with certainty which quaternary structural form of transthyretin is the amyloidogenic intermediate at this time. These difficulties arise because the maximal rate of fibril formation occurs at pH 3.6 where tetramer, traces of dimer, and significant amounts of monomer are observed.(ABSTRACT TRUNCATED AT 250 WORDS)
journal_name
Biochemistryjournal_title
Biochemistryauthors
Colon W,Kelly JWdoi
10.1021/bi00151a036subject
Has Abstractpub_date
1992-09-15 00:00:00pages
8654-60issue
36eissn
0006-2960issn
1520-4995journal_volume
31pub_type
杂志文章相关文献
BIOCHEMISTRY文献大全abstract::A model cosolvent, ethanol, has profound and diversified effects on the amyloidogenic self-assembly of insulin, yielding spectroscopically and morphologically distinguishable forms of beta-aggregates. The alcohol reduces hydrodynamic radii of insulin molecules, decreases enthalpic costs associated with aggregation-pro...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi050281t
更新日期:2005-06-28 00:00:00
abstract::Clustering of anionic lipids away from zwitterionic ones by cationic antimicrobial agents has recently been established as a mechanism of action of natural small, flexible peptides as well as non-natural synthetic peptide mimics. One of the largest classes of antimicrobial peptides consists of peptides that form catio...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi100378m
更新日期:2010-05-18 00:00:00
abstract::We investigated the effects of substituting two of the four tryptophans (the "inner pair" Trp(9) and Trp(11) or the "outer pair" Trp(13) and Trp(15)) in gramicidin A (gA) channels. The conformational preferences of the doubly substituted gA analogues were assessed using circular dichroism spectroscopy and size-exclusi...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi200136e
更新日期:2011-06-07 00:00:00
abstract::In efforts to understand the mechanisms of many nucleic acid enzymes, the first site-directed mutations are made at conserved acidic active residues. Almost without exception, the low or null activities of the resulting variants are attributed to the importance of the acidic residue(s) to the ligation of required meta...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi000337d
更新日期:2000-09-05 00:00:00
abstract::Eukaryotic translation initiation factor 2B (eIF2B) is the guanine nucleotide exchange factor of the GTPase eIF2, which brings the initiator Met-tRNAi to the ribosome in the form of the eIF2-GTP·Met-tRNAi ternary complex (TC). The activity of eIF2B is inhibited by phosphorylation of its substrate eIF2 by several stres...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/acs.biochem.7b00957
更新日期:2018-03-06 00:00:00
abstract::We describe a method for isolating milligram quantities of assembly-competent tubulin from the budding yeast Saccharomyces cerevisiae. The tubulin is > 95% purified and free of contaminating enzyme activities. As a result, it has been possible to determine the yeast tubulin equilibrium-binding constant for Mg-GTP and ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00085a013
更新日期:1993-08-31 00:00:00
abstract::Difference Fourier transform infrared spectra of lumirhodopsin, metarhodopsin I, and metarhodopsin II versus rhodopsin were recorded with hydrated films of bovine rod outer segments at 200, 240, and 270 K. In the region between 3700 and 3450 cm-1, the O-H stretching vibrational bands of water were identified by H(2)18...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00096a013
更新日期:1993-11-16 00:00:00
abstract::We report the first experimental characterization of the full thermodynamic profile for binding of urea to a native protein. We measured the volumetric parameters of lysozyme at pH 7.0 as a function of urea within a temperature range of 18-45 °C. At neutral pH, lysozyme retains its native conformation between 0 and 8 ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/acs.biochem.6b00805
更新日期:2016-11-29 00:00:00
abstract::Phe-tRNAPhe species modified on the 3'-terminal ribose residue were investigated for their ability to participate in individual steps of the elongation cycle using eukaryotic ribosomes from reticulocytes. None of the Phe-tRNAs used, namely Phe-tRNAPhe-C-C-3'dA, Phe-tRNAPhe-C-C-3'-NH2A, and Phe-tRNAPhe-C-C-Aoxi-red, ca...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00661a035
更新日期:1976-08-10 00:00:00
abstract::FixL is a heme-based oxygen-sensing histidine kinase that induces the expression of nitrogen fixation genes under hypoxic conditions. Oxygen dissociation from heme iron in the sensor domain of FixL initiates protein conformational changes that are transmitted to the histidine kinase domain, activating autophosphorylat...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/acs.biochem.6b00405
更新日期:2016-07-26 00:00:00
abstract::The kinetics and thermodynamics of Al(III) exchange between aluminum citrate (AlL) and human serum transferrin were investigated in the 7.2-8.9 pH range. The C-site of human serum apotransferrin in interaction with bicarbonate removes Al(III) from Al citrate with an exchange equilibrium constant K1 = (2.0 +/- 0.6) x 1...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi020627p
更新日期:2003-03-18 00:00:00
abstract::Metallo-beta-lactamases are a newly characterized family of zinc enzymes present in several pathogenic strains that represent an emerging clinical threat. Enzymes from different organisms exhibit an outstanding functional diversity, particularly in the metal ion requirements for activity. We have investigated the effe...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi010933n
更新日期:2002-02-12 00:00:00
abstract::Although the mechanism by which the steroidogenic acute regulatory protein (StAR) promotes steroidogenesis has been studied extensively, it remains incompletely characterized. Because structural analysis has revealed a hydrophobic sterol-binding pocket (SBP) within StAR, this study sought to examine the regulatory rol...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi401125v
更新日期:2013-10-15 00:00:00
abstract::The third intracellular loop (IL3) of G protein-coupled receptors (GPCRs) is an important contact domain between GPCRs and their G proteins. Previously, the IL3 of Ste2p, a Saccharomyces cerevisiae GPCR, was suggested to undergo a conformational change upon activation as detected by differential protease susceptibilit...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi200254h
更新日期:2011-08-16 00:00:00
abstract::alpha-1,3-Fucosyltransferase V (FucT V) catalyzes the transfer of 1-fucose from the donor sugar guanosine 5'-diphospho-beta-1-fucose (GDP-Fuc) to an acceptor sugar. A secondary isotope effect on the fucosyltransfer reaction with guanosine 5'-diphospho-[1-2H]-beta-1-fucose (GDP-[1-2H]-Fuc) as the substrate was observed...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi962284z
更新日期:1997-01-28 00:00:00
abstract::Bactenecin 5 and its fragments [BN22 (1-22), BN16 (7-22), and BC24 (20-43)] were synthesized by solid-phase methods. Their antifungal activities on Candida albicans have been studied and compared with those of the native bactenecin 5. The conformational preferences of these peptides in aqueous and nonaqueous solutions...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi951681r
更新日期:1996-04-09 00:00:00
abstract::Coordinate regulation of PARP-1 and -2 and PARG is required for cellular responses to genotoxic stress. While PARP-1 and -2 are regulated by DNA breaks and covalent modifications, mechanisms of PARG regulation are poorly understood. We report here discovery of a PARG regulatory segment far removed linearly from residu...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi100973m
更新日期:2010-09-07 00:00:00
abstract::The only identified component of the scrapie prion is PrPSc, a glycosylinositol phospholipid (GPI)-linked protein that is derived from the cellular isoform (PrPC) by an as yet unknown posttranslational event. Analysis of the PrPSc GPI has revealed six different glycoforms, three of which are unprecedented. Two of the ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00136a600
更新日期:1992-06-02 00:00:00
abstract::The guanidine hydrochloride- (GuHCl-) induced unfolding and refolding of a recombinant domain of bovine microsomal cytochrome b(5) containing the first 104 amino acid residues has been characterized by both transient and equilibrium spectrophotometric methods. The soluble domain is reversibly unfolded and the equilibr...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi991413j
更新日期:1999-10-26 00:00:00
abstract::We have modified the cytochrome b subunit of the cytochrome bc1 complex from the purple bacterium Rhodobacter sphaeroides to introduce two distinctive features of cytochrome b6 f complexes. In the first one, we have split cyt b into two polypeptides thus mimicking the organization of cyt b6 and subunit IV in the b6 f ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi9813476
更新日期:1998-11-17 00:00:00
abstract::Protein-protein interactions mediate the vast majority of cellular processes. Though protein interactions obey basic chemical principles also within the cell, the in vivo physiological environment may not allow for equilibrium to be reached. Thus, in vitro measured thermodynamic affinity may not provide a complete pic...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/acs.biochem.8b00172
更新日期:2018-08-07 00:00:00
abstract::The influenza virus RNA-dependent RNA polymerase protein complex contains an associated RNA endonuclease activity, which cleaves host mRNA precursors in the cell nucleus at defined positions 9-15 nucleotides downstream of the cap structure. This reaction provides capped oligoribonucleotides, which function as primers ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi9828932
更新日期:1999-04-27 00:00:00
abstract::The equilibrium binding of hemoglobin to isolated band 3 protein exhibited positive cooperativity [Hill coefficient = 1.65 +/- 0.1; total number of binding sites at pH 6.6 in 5 mM sodium phosphate buffer = 32 500 +/- 940 pmol/mg; Ka = (3.0 +/- 0.5) X 10(5) M-1]. The binding was reversible and ionic in nature as the bo...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00359a054
更新日期:1986-06-03 00:00:00
abstract::Oligodeoxynucleotides (ODNs) were conjugated to chlorambucil and used as affinity labeling reagents to study joint molecule formation by the Escherichia coli recombinase recA. Chlorambucil is a bifunctional nitrogen mustard which alkylates the N-7 position of guanine in the major groove of double-stranded DNA (dsDNA)....
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00040a022
更新日期:1995-10-10 00:00:00
abstract::A peptide consisting of the first 21 residues of human myelin basic protein (MBP) was synthesized. The N-terminal alanine of portions was blocked in separate experiments with alkyl carboxylates varying in size from 2 to 10 carbon atoms. The effects of these different alkyl carboxylates at the N-terminus on the seconda...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00180a008
更新日期:1994-04-12 00:00:00
abstract::Cofilin is an actin regulatory protein that binds to both monomeric and filamentous actin, and has filament severing activity. Although crystal structures for the monomeric forms of both G-actin and cofilin have been described, the structure of the binary cofilin-G-actin complex is not available. Synchrotron protein f...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi0121104
更新日期:2002-05-07 00:00:00
abstract::A combined N- and C-terminal truncation variant of human apolipoprotein A-I (apoA-I) was designed, expressed in Escherichia coli, isolated, and characterized. Hydrodynamic experiments yielded a weight average molecular weight of 34000, indicating apoA-I-(44-186) exists in solution predominantly as a dimer. An axial ra...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi0477135
更新日期:2005-03-22 00:00:00
abstract::Tropomyosin (TM) is a coiled-coil that binds head-to-tail along the helical actin filament. The ends of 284-residue tropomyosins are believed to overlap by about nine amino acids. The present study investigates the function of the N- and C-terminal overlap regions. Recombinant tropomyosins were produced in Escherichia...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi000242b
更新日期:2000-06-13 00:00:00
abstract::β-2-Microglobulin (β2m) forms amyloid fibrils in the joints of patients undergoing dialysis treatment as a result of kidney failure. One of the ways in which β2m can be induced to form amyloid fibrils in vitro is via incubation with stoichiometric amounts of Cu(II). To better understand the structural changes caused b...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/acs.biochem.6b01198
更新日期:2017-02-28 00:00:00
abstract::During fertilization, free-swimming mouse sperm bind to mZP3 (approximately 83 000 Mr), one of three zona pellucida glycoproteins, and once bound undergo the acrosome reaction, a type of cellular exocytosis [Wassarman, P. M., & Litscher, E. S. (1995) Curr. Top. Dev. Biol. 30, 1-19]. Sperm recognize and bind to specifi...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi952722m
更新日期:1996-04-02 00:00:00