Showing papers in "Journal of Molecular Biology in 2008"

TL;DR: It is shown that Sirt3 can deacetylate and thereby activate a central metabolic regulator in the mitochondrial matrix, glutamate dehydrogenase, and that the N- and C-terminal regions of Sirt 3 regulate its activity against glutamate dehydrogensase and a peptide substrate, indicating roles for these regions in substrate recognition and Sirtuin regulation.

TL;DR: It is shown that activation protein 1 (AP-1) activates the miR-21 transcription in conjugation with the SWI/SNF complex, after PMA stimulation, through the conserved AP-1 and PU.1 binding sites in the promoter identified here.

TL;DR: The results show not only that the regions of a protein with a high intrinsic aggregation propensity can be identified in a robust manner but also that the structural context of such regions in the monomeric form is crucial for determining their actual role in the aggregation process.

TL;DR: Allostery is essential for controlled catalysis, signal transmission, receptor trafficking, turning genes on and off, and apoptosis, and current data indicate that while side chains can reorient and rewire, allostery may not even involve a change of (backbone) shape.

TL;DR: This work implements a backrub-inspired sampling method in the Rosetta structure prediction and design program and suggests that backrub sampling captures a sizable fraction of localized conformational changes that occur in natural proteins.

TL;DR: It is found that compaction is regulated in two steps: Introduction of H4 acetylated to 30% on K16 inhibits compaction to a greater degree than deletion of the H4 N-terminal tail, and further decompaction is achieved by removal of the linker histone.

TL;DR: It is concluded that pausing is due to charge-specific interactions between the tunnel and the nascent peptide, and experimental evidence is provided that extraribosomal mechanisms do not account for this charge- specific pausing.

TL;DR: Thermodynamic changes arising from small differences between ligands binding to individual proteins are relatively large and, in general, uncorrelated with changes in solvation, suggesting that trends identified across widely differing proteins are of limited use in explaining or predicting the effects of ligand modifications.

TL;DR: HuCAL GOLD was challenged with a variety of different antigens and proved to be a reliable source of high-affinity human antibodies with best affinities in the picomolar range, thus functioning as an excellent source of antibodies for research, diagnostic, and therapeutic applications.

TL;DR: It is demonstrated that molecular titration can generate ultrasensitivity on timescales compatible with most cell-fate decisions, and it is suggested that dominant negatives are abundant in gene regulatory circuits and might be generating an ultrasensitive response in these networks.

TL;DR: SRP phage display is harnessed to generate a phage DARPin library containing more than 10 individual members and is able to select well behaved and highly specific DARPins against a broad range of target proteins having affinities as low as 100 pM directly from this library, without affinity maturation.

TL;DR: The coarse-grained models and effective energy functions for simulating thermodynamic and structural properties of multiprotein complexes with relatively low binding affinity and the interactions between ubiquitin and Vps27 are found to be positively cooperative, resulting in a substantial enhancement of the overall binding affinity beyond the approximately 300 microM of the specific domains.

TL;DR: The findings indicate the unique features of large, polymorphic neutral ensembles generated under high mutational loads and prompt the speculation that the progenitors of today's proteins may have evolved under highmutational loads.

TL;DR: It is concluded that the red-shifted spectral species represents the open channel state, and the thermal relaxation of this intermediate, the transition from P(3) to P(4), is coupled to channel closing.

TL;DR: It is proposed that long-enough ribosomal pause time scales may lead to alternate folding pathways and distinct minima on the folding free energy surface, leading to kinetically trapped states with altered structures and functions.

TL;DR: The results provide a structural basis for the complementary roles of these glycosyl hydrolase family 31 subunits in the bioprocessing of complex starch structures into glucose.

TL;DR: The results provide the first crystal structure of a natural bilirubin pigment bound to serum albumin, challenge some of the present conceptions about HSA–bilirubsin interactions, and provide a sound structural framework for finally resolving the long-standing question of where 4Z,15Z-bilirUBin-IXα binds to the protein.

TL;DR: The results suggest that drugs stabilizing alpha-helical Abeta conformers (or destabilizing the beta-sheet state) would block formation of neurotoxic oligomers, and the atomic-resolution conformer structures determined in the simulations may serve as useful targets for this purpose.

TL;DR: Knowledge of the effects of cofilin on actin filament bending mechanics, together with the previous analysis of torsional stiffness, provide a quantitative measure of the mechanical changes in actin filaments associated with co filin binding, and suggest that the overall mechanical and force-producing properties of cells can be modulated by cofilIn activity.

TL;DR: It is shown that the N-terminal domain of human Dicer, which is homologous to DExD/H-box helicases, substantially attenuates the rate of substrate cleavage and likely disrupts the functionality of the Dicer active site until a structural rearranged occurs.

TL;DR: The first structure for the glycoside hydrolase (GH) family 61 is presented, that of Cel61B from H. jecorina, and a structure-aided sequence alignment of all GH family 61 proteins identified a highly conserved group of residues on the surface of Cel 61B.

TL;DR: Experimental data indicate that NYAD-1 most likely targets capsid at a post-entry stage and may aid validation of capsid as an anti-HIV-1 drug target and may help in designing peptidomimetics and small molecule drugs targeted to this protein.

TL;DR: It is found that Arg does not contribute generally to the affinity of naïve antigen-binding sites and is detrimental to specificity, which is consistent with studies of natural antibodies, which have shown that nonspecific, self-reactive antibodies are rich in Arg and other positively charged residues.

TL;DR: It is shown that release of this constraint at high Ca(2+) allows a second segment of troponin, probably representing parts of TnT or the Troponin core domain, to promote tropomyosin movement on actin to the Ca( 2+)-induced C-state location, a constrained, relaxing position onActin that inhibits myosin-crossbridge association.

TL;DR: These studies show that unstructured peptides, such as the BH3 domains, behave like their structured counterparts and can bind tightly and selectively in an enthalpically driven process.

TL;DR: Widespread occurrence of these susceptible H5N1 clade 2.2 influenza strains should be considered high-risk, because of their significantly lower threshold for acquiring human receptor specificity and, therefore, warrant increased surveillance and further study.

TL;DR: This work demonstrates that positive selection alone is sufficient to completely respecialize the cytochrome P450 for function on a nonnative substrate.

TL;DR: Analysis of intermediate populations revealed that loop length diversity, loop shuffling, and recursive mutagenesis of diverse populations are all critical components.

TL;DR: This study demonstrates that the analysis of the MIECs between peptides and the SH3 domain can successfully characterize the binding interface, and it provides a framework to derive integrated prediction models for different domain-peptide systems.

TL;DR: The X-ray structure of lipase A from Candida antarctica is reported, solved by single isomorphous replacement with anomalous scattering, and refined to 2.2-A resolution, providing a basis for understanding the enzyme's preference for acyl moieties with long, straight tails, and for its highly promiscuous acceptance of widely different alcohol and amine moieties.