Showing papers in "Journal of Molecular Biology in 2007"

TL;DR: A new method, based on chemical thermodynamics, is developed for automatic detection of macromolecular assemblies in the Protein Data Bank (PDB) entries that are the results of X-ray diffraction experiments, as found, biological units may be recovered at 80-90% success rate, which makesX-ray crystallography an important source of experimental data on macromolescular complexes and protein-protein interactions.

TL;DR: A physicochemical understanding of modified nucleoside contributions to the tRNA anticodon domain architecture and its decoding of the genome has advanced RNA world evolutionary theory, the principles of RNA chemistry, and the application of this knowledge to the introduction of new amino acids to proteins.

TL;DR: A reformulation of the Rosetta docking method that incorporates explicit backbone flexibility in protein-protein docking, based on a "fold-tree" representation of the molecular system, which seamlessly integrates internal torsional degrees of freedom and rigid-body degrees offreedom.

TL;DR: The development and characterization of motavizumab is reported, an ultra-potent, affinity-matured, humanized mAb derived from palivizumac, an affinity-enhanced mAb being investigated in pivotal clinical trials and offers precious insights into the improvement of other therapeutic mAbs.

TL;DR: The conformational ensembles of the Abeta40 and Abeta42 peptide monomers are characterized by using a combination of molecular dynamics and measured scalar data from NMR experiments to confirm the existence of structured regions within the otherwise flexible Abeta peptides.

TL;DR: This bi-Gaussian model provides an analytical description of the predicted distributions of mutational stability effects and comprises a novel tool for analyzing proteins and protein models, for simulating the effect of mutations under evolutionary processes, and a quantitative description ofmutational robustness.

TL;DR: This fully synthetic, minimalist library has essentially recapitulated the capacity of the natural immune system to generate high-affinity antibodies by systematically augmented the original binary library with additional levels of diversity and examined the effects.

TL;DR: Alchemical free energy calculations in explicit solvent to predict ligand binding in a model cavity in T4 lysozyme are applied, beginning with single poses from docking, then including multiple poses, additional protein conformational changes, and using an improved charge model.

TL;DR: A coarse grained model is employed to explore the interplay between protein structure, folding and function which is applicable to allosteric or non-allosteric proteins and it is demonstrated that local unfolding may be due, in part, to competing intra-protein interactions.

TL;DR: The energetics of protein folding determine the 3D structure of a folded protein, and major factors include the hydrophobic factor and van der Waals interactions together with peptide hydrogen bonds and peptide solvation.

TL;DR: The findings provide a structural rationale to the prior suggestions that many IUPs are specialized for functions realized by protein-protein interactions, and help explain the increased evolutionary conservation of IUP interface residues.

TL;DR: Structural insight into the mechanisms of affinity enhancement suggest that the glycoform-dependent ADCC enhancement is attributed to a subtle conformational alteration in a limited region of IgG1-Fc.

TL;DR: The crystal structure of the S100A8/S100A9)(2) heterotetramer is described, which explains the well known Zn(2+) binding activity of calprotectin, whose overexpression can cause strong dysregulation of zinc homeostasis with severe clinical symptoms.

TL;DR: An analysis of the structural location of the framework mutations suggests that randomization of some framework residues either by error-prone PCR or by design in a future library could increase affinities and the target binding spectrum.

TL;DR: Improvements to the treatment of helical objects as a string of single particles using electron cryo-microscopy are made and the observed differences suggest that the new model represents a different, more stable state of the virus, compared with the earlier published model.

TL;DR: The structure of the rhodopsin mutant N2C/D282C expressed in mammalian cells is determined; the first structure of a recombinantly produced G protein-coupled receptor (GPCR) and the problems encountered during structure determination of GPCRs and other mammalian membrane proteins are shown.

TL;DR: The C-terminal domain (CTD) of the SARS-CoV nucleocapsid protein had stronger nucleic acid-binding activity than the NTD, and the crystal structure of the NP248-365 region was solved, suggesting a mechanism for helical RNA packaging in the virus.

TL;DR: The three-dimensional structure of the LOV domain of YtvA in its dark and light states is reported, which differs from plant phototropins and more closely resembles prokaryotic heme-binding PAS domains.

TL;DR: To investigate the alpha-synuclein protein and its role in Parkinson's disease, a library of random point mutants both in vitro and in yeast was screened to find variants in an unbiased way that could help to understand the sequence-phenotype relationship.

TL;DR: It is shown that in addition to domain folding, correct inter-domain assembly is essential to form a stable unit that satisfies endoplasmic reticulum (ER) quality control and that the catalytically crucial inter-NBD associations are not required to satisfy ER quality control mechanisms.

TL;DR: It is suggested that to increase protein solubility, asparagine, glutamine, or threonine should be replaced with aspartic acid, glutamic acid or serine, especially at high net charge.

TL;DR: A striking correlation was observed for relative binding affinities towards ifnar1 and ifnar2 with the differential antiproliferative potency and this correlation was confirmed by systematically engineering IFNalpha2 mutants with very high differential antiprology potency.

TL;DR: This study suggests that SARS-CoV Mpro could serve as a new tag-cleavage endopeptidase for protein overproduction, and the WT SARS/WT Mpro is more appropriate for mechanistic characterization and inhibitor design.

TL;DR: It is shown that pockets binding the same ligand show greater variation in their shapes than can be accounted for by the conformational variability of the ligand, suggesting that geometrical complementarity in general is not sufficient to drive molecular recognition.

TL;DR: The close correspondence between the predicted and observed nucleosome locations demonstrates the potential advantage of the "structural" approach in the computer mapping of nucleosomes positioning.

TL;DR: The use of FRET has enabled direct observation of intersub unit movement in solution, provides independent evidence that formation of the hybrid state is coupled to rotation of the 30 S subunit and shows that the intersubunit movement is reversed during the second step of translocation.

TL;DR: Examination of the effects of salt ions on the aggregation propensity of Alzheimer's Abeta(1-40) peptide and on the structure of the dissolved and of the fibrillar peptide suggests that there is no fully uniform way in which salts affect aggregation of different polypeptide chains.

TL;DR: It is demonstrated that lysozyme is not a single uniform species but rather a continuum of cross-beta-sheet-containing amyloids that are cytotoxic, indicating that amyloid toxicity should be assessed in all clinical applications involving proteinaceous materials.

TL;DR: The results indicate that cofilin severs the actin filament by a mechanism of allosteric and cooperative destabilization, which has particular relevance to co filin function during actin-based motility in cells and in synthetic systems.

TL;DR: A comprehensive kinetic mechanism is presented where all steps involving protein hydrolysis, fragmentation, assembly and conversion into amyloid fibrils are accounted for and it is shown that intact full-length lysozyme at the end of the lag phase slows the rate of amyloidsogenesis.