Abstract：
:The accumulation of senile plaques composed of amyloid β (Aβ) fibrils is a hallmark of Alzheimer's disease, although prefibrillar oligomeric species are believed to be the primary neurotoxic congeners in the pathogenesis of Alzheimer's disease. Uncertainty regarding the mechanistic relationship between Aβ oligomer and fibril formation and the cytotoxicity of these aggregate species persists. β-Turn formation has been proposed to be a potential rate-limiting step during Aβ fibrillogenesis. The effect of turn nucleation on Aβ self-assembly was probed by systematically replacing amino acid pairs in the putative turn region of Aβ (residues 24-27) with d-ProGly ((D)PG), an effective turn-nucleating motif. The kinetic, thermodynamic, and cytotoxic effects of these mutations were characterized. It was found that turn formation dramatically accelerated Aβ fibril self-assembly dependent on the site of turn nucleation. The cytotoxicity of the three (D)PG-containing Aβ variants was significantly lower than that of wild-type Aβ40, presumably due to decreased oligomer populations as a function of a more rapid progression to mature fibrils; oligomer populations were not eliminated, however, suggesting that turn formation is also a feature of oligomer structures. These results indicate that turn nucleation is a critical step in Aβ40 fibril formation.
journal_name
J Mol Bioljournal_title
Journal of molecular biologyauthors
Doran TM,Anderson EA,Latchney SE,Opanashuk LA,Nilsson BLdoi
10.1016/j.jmb.2012.01.055subject
Has Abstractpub_date
2012-08-10 00:00:00pages
315-28issue
2-3eissn
0022-2836issn
1089-8638pii
S0022-2836(12)00124-6journal_volume
421pub_type
杂志文章abstract：:The X-ray crystal structure of the Escherichia coli stress response protein HDEA has been determined at 2.0 A resolution. The single domain alpha-helical protein is found in the periplasmic space, where it supports an acid resistance phenotype essential for infectivity of enteric bacterial pathogens, such as Shigella ...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.1999.3347
更新日期：2000-01-21 00:00:00
abstract：:Mammalian hosts interface intimately with commensal and pathogenic bacteria. It is increasingly clear that molecular interactions between the nervous system and microbes contribute to health and disease. Both commensal and pathogenic bacteria are capable of producing molecules that act on neurons and affect essential ...
journal_title：Journal of molecular biology
pub_type： 杂志文章,评审
doi：10.1016/j.jmb.2016.12.023
更新日期：2017-03-10 00:00:00
abstract：:HtrA (high-temperature requirement A) family proteins play important roles in protein-quality control processes in the bacterial periplasm. A common feature of all members of this family is their modular organization comprising a chymotrypsin-like protease domain and at least one PDZ (postsynaptic density of 95 kDa, d...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2015.06.023
更新日期：2015-08-28 00:00:00
abstract：:Collagen fibrils are the principle source of mechanical strength in the mutable dermis of the sea cucumber Cucumaria frondosa. To obtain information about the mechanism by which collagen molecules self-assemble into fibrils, we have isolated single intact fibrils with lengths in the range 14-444 microm. These fibrils ...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.1998.2230
更新日期：1998-12-18 00:00:00
abstract：:RGG/RG motifs are RNA binding segments found in many proteins that can partition into membraneless organelles. They occur in the context of low-complexity disordered regions and often in multiple copies. Although short RGG/RG-containing regions can sometimes form high-affinity interactions with RNA structures, multipl...
journal_title：Journal of molecular biology
pub_type： 杂志文章,评审
doi：10.1016/j.jmb.2018.06.014
更新日期：2018-11-02 00:00:00
abstract：:Conserved structural and functional features of Cu,Zn superoxide dismutase enzymes have been studied by comparison of known three-dimensional structures and analysis of the currently available amino acid sequences. For this purpose, the three-dimensional structures of the bovine, spinach and yeast enzymes have been su...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.1994.1298
更新日期：1994-05-06 00:00:00
abstract：:Tumor suppressor p53 plays a central role in tumor suppression. p53 is the most frequently mutated gene in human cancer, and over half of human cancers contain p53 mutations. Majority of p53 mutations in cancer are missense mutations, leading to the expression of full-length mutant p53 (mutp53) protein. While the crit...
journal_title：Journal of molecular biology
pub_type： 杂志文章,评审
doi：10.1016/j.jmb.2017.03.030
更新日期：2017-06-02 00:00:00
abstract：:Rvb1 and Rvb2 are essential AAA(+) (ATPases associated with diverse cellular activities) helicases, which are important components of critical complexes such as chromatin remodeling and telomerase complexes. The oligomeric state of the Rvb proteins has been controversial. Independent studies from several groups have d...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2010.10.003
更新日期：2010-12-03 00:00:00
abstract：:The effect on translational pausing of a hydrophobic probe, coumarin, at the N terminus of nascent peptides was investigated. Two different proteins, bacterial chloramphenicol acetyltransferase and bovine rhodanese, were synthesized by coupled transcription/translation in a cell-free system derived from Escherichia co...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.1998.2481
更新日期：1999-02-12 00:00:00
abstract：:The yeast a1 and alpha 2 proteins are examples of homeodomain proteins that display cell-type-specific expression. They are co-expressed in only one type of cell, the a/alpha cell, where they repress the expression of a group of target genes. Using purified proteins, we demonstrate that a1 and alpha 2 form a highly sp...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.1993.1517
更新日期：1993-10-05 00:00:00
abstract：:An effective strategy for a plasmid to be maintained in a growing population of bacteria is to prevent the proliferation of newly formed daughter cells that lack the plasmid. In this study, we determined that the promiscuous, incompatibility group P plasmid RK2 encodes such a system. To induce large numbers of RK2-fre...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.1994.1208
更新日期：1994-03-18 00:00:00
abstract：:Cytosolic heat shock protein 90 (Hsp90) has been shown to be essential for many infectious pathogens and is considered a potential target for drug development. In this study, we have carried out biochemical characterization of Hsp90 from a poorly studied protozoan parasite of clinical importance, Entamoeba histolytica...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2014.01.008
更新日期：2014-04-17 00:00:00
abstract：:Intrinsically disordered proteins (IDPs) lack stable tertiary structure under physiological conditions. The unique composition and complex dynamical behaviour of IDPs make them a challenge for structural biology and molecular evolution studies. Using NMR ensembles, we found that IDPs evolve under a strong site-specifi...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2020.166751
更新日期：2021-02-05 00:00:00
abstract：:The development of electrostatic interactions during the folding of the N-terminal domain of the ribosomal protein L9 (NTL9) is investigated by pH-dependent rate equilibrium free energy relationships. We show that Asp8, among six acidic residues, is involved in non-native, electrostatic interactions with K12 in the tr...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2006.04.038
更新日期：2006-06-23 00:00:00
abstract：:The crystal structure of a construct consisting of the FERM and SH2-like domains of the human Janus kinase 1 (JAK1) bound to a fragment of the intracellular domain of the interferon-λ receptor 1 (IFNLR1) has been determined at the nominal resolution of 2.1Å. In this structure, the receptor peptide forms an 85-Å-long e...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2016.10.005
更新日期：2016-11-20 00:00:00
abstract：:We describe a hybrid statistical mechanical and dynamical approach for modelling the formation of closed, open and elongating complexes of RNA polymerase, the interactions of these polymerases to produce transcriptional interference, and the regulation of these processes by a DNA-binding and DNA-looping regulatory pro...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2007.04.041
更新日期：2007-06-22 00:00:00
abstract：:We used spin-labeled nucleotide analogs and fluorescence spectroscopy to monitor conformational changes at the nucleotide-binding site of wild-type Dictyostelium discoideum (WT) myosin and a construct containing a single tryptophan at position F239 near the switch 1 loop. Electron paramagnetic resonance (EPR) spectros...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2009.12.035
更新日期：2010-03-05 00:00:00
abstract：:Transcription initiation by the enhancer-dependent sigma(54) RNA polymerase holoenzyme is positively regulated after promoter binding. The promoter DNA melting process is subject to activation by an enhancer-bound activator protein with nucleoside triphosphate hydrolysis activity. Tethered iron chelate probes attached...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.2000.4393
更新日期：2001-03-02 00:00:00
abstract：:SpoIIAA is a key component in the network of interactions that regulate the first sporulation-specific transcription factor, sigma(F), in Bacillus subtilis. In its unphosphorylated form SpoIIAA is either phosphorylated by or forms a non-covalent complex with SpoIIAB, whereas in its phosphorylated form it is dephosphor...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.2001.5142
更新日期：2001-11-30 00:00:00
abstract：:Stereospecific conversion of hydantoins into their carbamoyl acid derivatives could be achieved by using the enzyme hydantoinase. Specific hydantoinases convert either the D-form or the L-form of the hydantoin and the amino acids responsible for stereospecificity have not been identified. Structural studies on hydanto...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2005.01.025
更新日期：2005-03-18 00:00:00
abstract：:Pyrimidine bases are the central precursors for RNA and DNA, and their intracellular pools are determined by de novo, salvage and catabolic pathways. In eukaryotes, degradation of uracil has been believed to proceed only via the reduction to dihydrouracil. Using a yeast model, Saccharomyces kluyveri, we show that duri...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2008.05.029
更新日期：2008-07-18 00:00:00
abstract：:In common with many other eukaryotic species, the genomes of species in the genus Allium contain a high proportion of repeated DNA sequences, which may be implicated in the considerable differences in genome size that are seen between even very closely related species. The gross organization of repetitive sequences wi...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/s0022-2836(83)80189-2
更新日期：1983-11-15 00:00:00
abstract：:Ribosomal subunit joining is a key checkpoint in the bacterial translation initiation pathway during which initiation factors (IFs) regulate association of the 30S initiation complex (IC) with the 50S subunit to control formation of a 70S IC that can enter into the elongation stage of protein synthesis. The GTP-bound ...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2014.09.024
更新日期：2015-05-08 00:00:00
abstract：:Previous studies show that some yeast strains carrying point mutations of domain 5 that block splicing of a mitochondrial group II intron yield spontaneous revertants in which splicing is partially restored by dominant mutations of nuclear genes. Here we cloned and sequenced the suppressor allele of one such gene, and...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.1998.2021
更新日期：1998-09-25 00:00:00
abstract：:Computational searches for DNA binding sites often utilize consensus sequences. These search models make assumptions that the frequency of a base pair in an alignment relates to the base pair's importance in binding and presume that base pairs contribute independently to the overall interaction with the DNA-binding pr...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2008.04.043
更新日期：2008-06-20 00:00:00
abstract：:The molecular chaperone Hsp90 and its cofactor Cdc37 are required for the stability of protein kinases in the cellular environment. Upon pharmacological inhibition of Hsp90, the Hsp90-dependent kinases are degraded quickly by the proteasome. Clear physiological evidence for the formation of heterooligomeric complexes ...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2016.09.002
更新日期：2016-10-09 00:00:00
abstract：:The p127 tumor suppressor protein encoded by the lethal(2)giant larvae, l(2)gl, gene of Drosophila melanogaster forms high molecular mass complexes consisting predominantly of p127 molecules. To determine whether p127 can self-assemble in the absence of other binding factors, we analyzed the size of in vitro synthesiz...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.1996.0656
更新日期：1996-12-06 00:00:00
abstract：:The folding kinetics and thermodynamics of the isolated C-terminal domain of the ribosomal protein L9 (CTL9) have been studied as a function of pH. CTL9 is an alpha-beta protein that contains a single beta-sheet with an unusual mixed parallel, anti-parallel topology. The folding is fully reversible and two-state over ...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/S0022-2836(02)00015-3
更新日期：2002-04-26 00:00:00
abstract：:Peptidyl-tRNA hydrolase cleaves the ester bond between tRNA and the attached peptide in peptidyl-tRNA in order to avoid the toxicity resulting from its accumulation and to free the tRNA available for further rounds in protein synthesis. The structure of the enzyme from Mycobacterium tuberculosis has been determined in...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2007.06.053
更新日期：2007-09-07 00:00:00
abstract：:The Hepatitis C virus is a positive-stranded RNA virus which is the causal agent for a chronic liver infection afflicting more than 170,000,000 people world-wide. The HCV genome is approximately 9.6 kb in length and the proteome encoded is a polyprotein of a little more than 3000 amino acid residues. This polyprotein ...
journal_title：Journal of molecular biology
pub_type： 杂志文章,评审
doi：10.1006/jmbi.2001.5055
更新日期：2001-10-26 00:00:00
