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Showing papers in "Journal of Molecular Biology in 2012"


Journal ArticleDOI
TL;DR: A Bayesian interpretation of cryo-EM structure determination is described, where smoothness in the reconstructed density is imposed through a Gaussian prior in the Fourier domain, so that the optimal 3D linear filter is obtained without the need for arbitrariness and objective resolution estimates may be obtained.

760 citations


Journal ArticleDOI
TL;DR: This review focuses on the insights from classical and modern theories of linear growth phenomena and discusses how theory allows the roles of growth and nucleation processes to be defined through the analysis of experimental in vitro time courses of amyloid formation.

415 citations


Journal ArticleDOI
TL;DR: Focusing primarily on the oligomeric states formed from Alzheimer's disease β-amyloid (Aβ) peptide, this review will make references to other polypeptide systems, highlighting common principles or sequence-specific differences.

318 citations


Journal ArticleDOI
TL;DR: The biophysical basis for the kinetic stabilization strategy and the structure-based drug design effort that led to this first-in-class pharmacologic agent are reviewed.

288 citations


Journal ArticleDOI
TL;DR: This review covers research on intervention of amyloidosis and highlights several examples of how inhibition of protein aggregation and amyloids formation has been achieved in practice.

262 citations


Journal ArticleDOI
TL;DR: The plasmids pDusk and pDawn as mentioned in this paper employ blue-light photoreceptors to induce light-repressed or light-induced gene expression in Escherichia coli with up to 460fold induction upon illumination.

196 citations


Journal ArticleDOI
TL;DR: It is concluded that both PE and CL are required for a full activity of the mitochondrial respiratory chain and the efficient generation of the inner membrane potential.

193 citations


Journal ArticleDOI
TL;DR: An FN3 library is reported that utilizes alternative positions for presenting amino acid diversity on a β-sheet and surface loops that together form a concave surface and produced binding proteins to multiple target proteins with similar efficacy as the original, loop-focused library.

192 citations


Journal ArticleDOI
TL;DR: A metric to predict organism-specific relative translation rates of codons based on the availability of tRNA decoding mechanisms: Watson-Crick, non-Watson-Cricks or both types of interactions is developed and it is demonstrated that sequence harmonization based on expression host tRNA pools, designed to mimic ribosome movement of the original organism, can significantly increase the folding of the encoded polypeptide.

189 citations


Journal ArticleDOI
TL;DR: The nicotinic acetylcholine (ACh) receptor converts transiently to an open-channel form when activated by ACh released into the synaptic cleft, determined by electron microscopy of ACh-sprayed and freeze-trapped postsynaptic membranes.

181 citations


Journal ArticleDOI
TL;DR: The 2.9-Å-resolution structure of the DNA cleavage core of human topoisomerase IIα (TOP2A) bound to a doubly nicked, 30-bp duplex oligonucleotide is determined and reveals that the principal site of DNA engagement undergoes highly quantized conformational transitions between distinct binding, cleavage, and drug-inhibited states that correlate with the control of subunit-subunit interactions.

Journal ArticleDOI
TL;DR: The use of very short polyQ repeat lengths in htt N-terminal fragments to slow this disease-associated aggregation is described, based on a regular pattern of multimers observed in analytical ultracentrifugation, and a concentration dependence of α-helix formation in CD spectroscopy.

Journal ArticleDOI
TL;DR: This review summarizes experimental and computational studies on the solution structure and aggregation properties of both simple and complex polyQ sequences, and their repeat-length dependence.

Journal ArticleDOI
TL;DR: The generality of the approach is demonstrated and it is shown that these bispecific antibodies have properties similar to those of wild-type IgGs, and the utility of the technology is demonstrated with an example of a CD3/CD20 bispespecific antibody that effectively depletes B cells in vitro and in vivo.

Journal ArticleDOI
TL;DR: It is found that EGCG interferes with the aromatic hydrophobic core of Aβ, and the structural analysis of small-molecule-induced amyloid aggregates will open new perspectives for Alzheimer's disease drug development.

Journal ArticleDOI
TL;DR: PON1's active site shows a remarkable level of networking and versatility whereby multiple residues share the same task and individual active-site residues perform multiple tasks (e.g., binding the catalytic calcium and activating the hydrolytic water).

Journal ArticleDOI
TL;DR: In Lemo21(DE3), the modulation of the activity of the T7 RNAP by the T 7 lysozyme is key to optimizing the ratio of membrane proteins properly inserted in the cytoplasmic membrane to non-inserted proteins.

Journal ArticleDOI
TL;DR: The molecular investigation of the amyloidoses began in the mid-19th century with the observation of areas in human tissues obtained at autopsy that were homogeneous and eosinophilic with conventional stains but became blue when exposed to mixtures of iodine and sulfuric acid.

Journal ArticleDOI
TL;DR: Insight is provided into the structure and function of the CBM33 family of enzymes, which, together with their fungal counterpart called GH61, currently receive considerable attention in the biomass processing field.

Journal ArticleDOI
TL;DR: This review summarizes the elements of the phagemids and their corresponding functions and the possible trends and future direction to improve the characteristics of thePhagemid.

Journal ArticleDOI
TL;DR: Recent discoveries that identify Spt5-like factors as evolutionary conserved nexus for the regulation and coordination of the machineries responsible for information processing in the cell are discussed.

Journal ArticleDOI
TL;DR: The grass Lolium perenne produces an ice-binding protein (LpIBP) that helps this perennial tolerate freezing by inhibiting the recrystallization of ice, and the first crystal structure of a plant IBP is solved.

Journal ArticleDOI
Xiang Yu1, Jie Zheng1
TL;DR: In this article, the effect of cholesterol levels on the interaction of amyloid-β (Aβ) with the zwitterionic 1-palmitoyl-2-oleoylphosphatidylcholine (POPC) bilayer containing different mole fractions of cholesterol from χ=0, 02, to 04 using all-atom molecular dynamics simulations.

Journal ArticleDOI
TL;DR: These findings provide a framework to rationalize the LOV domain architecture, as well as the signaling mechanisms in both isolated and tandem arrangements of PAS domains, and can be applied in engineering LOV-based photoswitches, opening up new design strategies and improving existing ones.

Journal ArticleDOI
TL;DR: High-speed atomic force microscopy (HS-AFM) visualizes the dynamic molecular processes of isolated proteins at sub-molecular resolution without the need for complicated sample preparation and is reported for the first time the direct observation of dynamic molecular architectures on a live cell surface.

Journal ArticleDOI
Jason Greenwald1, Roland Riek1
TL;DR: The aim of this short essay is to discuss the hypothesis that one type of protein aggregate-the cross-β-sheet motif-was the first functional protein fold, that is, the common ancestor fold.

Journal ArticleDOI
TL;DR: The three-dimensional structure of human GALNS is reported, which establishes the molecular basis for MPS IV A and for the larger MPS family of diseases.

Journal ArticleDOI
TL;DR: The program PCS-ROSETTA automatically determines the Δχ-tensor and metal position from the PCS data during the structure calculations, without any prior knowledge of the protein structure, offering a powerful new approach to protein structure determination.

Journal ArticleDOI
TL;DR: This work engineered a linear-linkage-specific antibody that is functional in Western blot, immunoprecipitation, and immunofluorescence applications and uses the antibody to demonstrate that linear polyUb is up-regulated upon tumor necrosis factor α stimulation of cells, consistent with a critical role in nuclear factor κB signaling.

Journal ArticleDOI
TL;DR: Investigation of the effect of lipid head group charges on the signal transduction properties of the class A GPCR neurotensin (NT) receptor 1 (NTS1) under defined experimental conditions demonstrates that negatively charged lipids in the immediate vicinity of a nonvisual GPCRs modulate the G-protein-coupling step.