Abstract
We have performed a series of molecular dynamics simulations of ERK1 and -2 in various stages of activation as well as the constitutively active Q103A, I84A, L73P, and R65S ERK2 mutants. Our simulations indicate the importance of domain closure for autoactivation and activity regulation, with that e...
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PMID: 21842857
PDF is available here.
Abstract
We show that Rrn7, a subunit of the yeast Pol I core factor, and its human ortholog TAF1B are TFIIB-like factors. Although distantly related, Rrn7 shares many activities associated with TFIIB-like factors. Domain swaps between TFIIB-related factors show that Rrn7 is most closely related to the Pol I...
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PMID: 21921198
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Abstract
We report that TAF1B, a subunit of human Pol I basal transcription factor SL1, is structurally related to TFIIB/TFIIB-like proteins, through predicted amino-terminal zinc ribbon and cyclin-like fold domains. SL1, essential for Pol I recruitment to the ribosomal RNA gene promoter, also has an essenti...
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PMID: 21921199
PDF is available here.
Abstract
We determined the structure of Phytophthora capsici AVR3a4, a close homolog of P. infestans AVR3a. Our structural and functional analyses reveal that the effector domain of AVR3a contains a conserved, positively charged patch and that this region, rather than the RXLR domain, is required for binding...
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PMID: 21821794
PDF is available here.
Abstract
GuHCl-induced denaturation of human plasma apoA-I, apoA-II, apoA-IV, apoE3 and three recombinant apoE isoforms in solution and discoidal complexes with phosphatidylcholine (only plasma proteins) was studied. The protein conformational stability (ΔG(H(2)O)) and a slope of linear depe...
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PMID: 21600318
PDF is available here.
Abstract
We have undertaken an extensive structural analysis of proteins containing CUG-encoded residues and solved the crystal structures of the two natural isoforms of Candida albicans seryl-tRNA synthetase. We show that codon reassignment resulted in a nonrandom genome-wide CUG redistribution tailored to...
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PMID: 21825144
PDF is available here.
Abstract
We recently introduced the enhanced aromatic sequon as a family of portable structural motifs that are stabilized upon glycosylation in specific reverse turn contexts: a five-residue type I β-turn harboring a G1 β-bulge (using a Phe-Yyy-Asn-Xxx-Thr sequon) and a type II β-turn within a six-residu...
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PMID: 21825145
PDF is available here.
Abstract
We determined the structure of the hydrophilic domain. Here we report the crystal structure of the Esherichia coli complex I membrane domain at 3.0 Å resolution. It includes six subunits, NuoL, NuoM, NuoN, NuoA, NuoJ and NuoK, with 55 transmembrane helices. The fold of the homologous antiporter-l...
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PMID: 21822288
PDF is available here.
Abstract
We conducted two genome-wide RNAi screens identifying genes required for intoxication and demonstrating that requirements are strikingly different between PE and Ricin, with only 13% overlap. Yet factors required by both toxins are present from the endosomes to the ER, and, at the morphological leve...
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PMID: 21782526
PDF is available here.
Abstract
We review here the current knowledge and show that Prxs can be effectively classified by a structural/evolutionary organization into six subfamilies followed by specification of a 1-Cys or 2-Cys mechanism, and for 2-Cys Prxs, the structural location of the resolving Cys. We visualize the varied cata...
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PMID: 20969484
PDF is available here.
Abstract
We discuss the spatial and temporal organization of cellular quality control strategies and their implications for human diseases linked to protein misfolding and aggregation....
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PMID: 21746797
PDF is available here.
Abstract
We present examples of proteins where changes in stability results in changes in affinity and of proteins where stability and affinity are uncorrelated. We discuss the possibility for a relationship between stability and binding. From the data presented is it clear that there are specific sites (fle...
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PMID: 21094283
PDF is available here.
Abstract
We dissect the folding mechanism of the α-helical molten-globular protein NCBD from three fundamentally different approaches: statistical-mechanical variable barrier model, Cα-based Gō-model and explicit water all-atom molecular dynamics (MD) simulations. We find that NCBD displays the characteri...
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PMID: 21732676
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Abstract
We analyzed the possible relationship between the protein folding rates and the corresponding mRNA sequences. The content of guanine and cytosine (GC content) of palindromes in protein coding sequence was introduced as a new parameter and added in the Gromiha's model of predicting protein folding ra...
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PMID: 21613670
PDF is available here.
Abstract
We discuss the various modes of intramembrane protein-lipid interactions in cellular membranes, including examples for both annular and nonannular bound lipids. Furthermore, we will discuss possible functional roles of such specific protein-lipid interactions as well as roles of lipids as chaperones...
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PMID: 21536707
PDF is available here.
Abstract
In the cell, protein folding into stable globular conformations is in competition with aggregation into non-functional and usually toxic structures, since the biophysical properties that promote folding also tend to favor intermolecular contacts, leading to the formation of β-sheet-...
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PMID: 21538897
PDF is available here.
Abstract
We will address how protein homeostasis (proteostasis) is achieved at the level of the cell and organism, and how the threshold of the stress response is set to detect and combat protein misfolding. For metazoans, the requirement for coordinated function and growth imposes additional constraints on...
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PMID: 21536706
PDF is available here.
Abstract
Neuroinflammation is a pathological hallmark of neurodegenerative diseases including amyotrophic lateral sclerosis (ALS), and is characterized by activated microglia at sites of neuronal injury. In ALS, neurons do not die alone; neuronal injury is noncell-autonomous and depends upon a well-orchestrat...
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PMID: 21842586
PDF is available here.
Abstract
I and II chaperonins, mainly in the molecular rearrangements that take place during the functional cycle. These differences are evident for the most complex chaperonin, the eukaryotic cytosolic CCT, which highlights the uniqueness of this important molecular machine.
Copyright © 201...
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PMID: 21723731
PDF is available here.
Abstract
The twin-arginine translocase (Tat) system is used by many bacteria and plants to move folded proteins across the cytoplasmic or thylakoid membrane. In most bacteria, the TatA protein is believed to form a defined pore in the membrane through homo-oligomerization with other TatA protomers. The predic...
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PMID: 21683683
PDF is available here.
Abstract
We studied the effects of a chemically modified β-CD (BCD07056), on the aggregating and refolding properties of BlaPChBD, a hybrid protein obtained by inserting the chitin binding domain of the human macrophage chitotriosidase into the class A β-lactamase BlaP from Bacillus licheniformis 749/I dur...
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PMID: 21621654
PDF is available here.
Abstract
We combine all-atom molecular dynamics and coarse-grain Brownian dynamics to establish a complete mechanical landscape for six different globins chain (myoglobin, neuroglobin, cytoglobin, truncated hemoglobin, and chains α and β of hemoglobin). We show that the rigidity profiles of these proteins...
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PMID: 21553890
PDF is available here.
Abstract
We describe here our experience with site-specific protein modification via a novel cysteine-containing fusion tag (Cys-tag), which is a 15-amino-acid (aa) N-terminal fragment of human ribonuclease I with the R4C substitution. Several Cys-tagged proteins and peptides with different numbers of native...
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PMID: 18726580
PDF is available here.
Abstract
We present an automated tool, SimGlycan, for this purpose, which accepts raw/standard MS data files as input and characterizes the associated glycan structure with high accuracy using database searching and scoring techniques. Not only does it predict the glycan structure using an MS/MS database sea...
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PMID: 19882135
PDF is available here.
Abstract
From exponentially large numbers of possible sequences, protein design seeks to identify the properties of those that fold to predetermined structures and have targeted structural and functional properties. The interactions that confer structure and function involve intermolecular forces and large nu...
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PMID: 21128762
PDF is available here.
Abstract
We cover both key developments in the field and potential future directions. Additionally, particular emphasis is given to two general approaches, namely the renormalization and reference potential approaches, which allow one to move back and forth between the coarse-grained (CG) and full models, as...
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PMID: 21034218
PDF is available here.
Abstract
We show that a variety of theoretical approaches, ranging from scaling arguments to minimal models to atomistic simulations, are needed as a complement to experimental studies probing the principles governing protein aggregation....
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PMID: 21219143
PDF is available here.
Abstract
We established the molecular basis for this model for the archetypal signaling adaptor protein Crk-II by measuring the thermodynamics and kinetics of the equilibrium between autoinhibited and activated-like states. We used fluorescence and NMR spectroscopies together with segmental isotopic labeling...
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PMID: 21532593
PDF is available here.
Abstract
Aging cells accumulate damaged and misfolded proteins through a functional decline in their protein homeostasis (proteostasis) machinery, leading to reduced cellular viability and the development of protein misfolding diseases such as Alzheimer's and Huntington's. Metabolic signaling...
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PMID: 21441594
PDF is available here.
Abstract
We have carried out a spectroscopical/structural characterization of the recombinant ectodomain in order to obtain information on its dynamic structure in solution and on its ability to form homodimers by itself in the absence of the transmembrane helix and of the potential interactions with the pla...
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PMID: 21352957
PDF is available here.
Abstract
We iteratively performed atomistic molecular dynamics simulations and biophysical measurements to probe the interaction of a cyclic antimicrobial peptide and its inactive linear analogue with model membranes. We establish that, relative to the linear peptide, the cyclic one binds stronger to negativ...
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PMID: 21586269
PDF is available here.
Abstract
The effects of chloride and sulfate salts of tetrapropylammonium (TPA(+)) and guanidinium (Gdm(+)) on the conformational stabilities of tryptophan zipper (trpzip) and α-helical (alahel) peptides were measured by circular dichroism spectroscopy. Like Gdm(+), TPA(+) interacts with the planar tryptopha...
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PMID: 21520945
PDF is available here.
Abstract
We have calculated the potential of mean force for α-helix formation of a 10-alanine oligopeptide as a function of its position within the translocon channel. We find that the predominant conformational states, α-helical and extended, reflect those found for the peptide in water. However, the tran...
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PMID: 21524073
PDF is available here.
Abstract
We have investigated the mutation effects on the structures and thermodynamics for the aggregation and folding of AcP by using the combination of fully atomistic, explicit-water molecular dynamics simulations, and three-dimensional reference interaction site model theory. The results indicate that t...
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PMID: 21500781
PDF is available here.
Abstract
We describe the molecular mechanisms regulating the ubiquitin proteasome system, thereby focussing on Nrf2 as well as on the recently identified transcription factor (TF) TCF11. In response to proteasome inhibition TCF11 plays a central role in upregulating the proteasome system via an ERAD-dependen...
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PMID: 21412055
PDF is available here.
Abstract
We used this strategy and obtained high expression levels of a chloroplast ATP/ADP transporter from A. thaliana (NTT1) and characterized its transport properties. NTT1 fused to Mistic has a very low transport activity which can be recovered after in vivo Mistic fusion cleavage. Moreover, detailed mo...
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PMID: 21550334
PDF is available here.
Abstract
Actinoporins constitute a group of small and basic α-pore forming toxins produced by sea anemones. They display high sequence identity and appear as multigene families. They show a singular behaviour at the water-membrane interface: In aqueous solution, actinoporins remain stably folded but, upon in...
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PMID: 21621507
PDF is available here.
Abstract
We study the folding pathway for purified LamB protein in detergent and observe extreme hysteresis in unfolding and refolding, as indicated by the shift in intrinsic fluorescence. The strong hysteresis is not seen in unfolding and refolding a mutant LamB protein lacking the disulfide bond, as it unf...
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PMID: 21640073
PDF is available here.
Abstract
We introduce Overhauser dynamic nuclear polarization at 0.35 T via site-specific nitroxide spin labels as a unique tool to probe internal and surface protein hydration dynamics with site-specific resolution in the molten globular, native, and unfolded protein states. The (1)H NMR signal enhancement...
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PMID: 21443207
PDF is available here.
Abstract
We have examined systematically the effects of protein size and sequence on the value of ΔV(u) using as a model system a series of deletion variants of the ankyrin repeat domain of the Notch receptor. The results provide strong evidence in support of the notion that the major contributing factor to...
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PMID: 21446709
PDF is available here.
Abstract
Intrinsically disordered proteins are highly abundant in nature and play a number of crucial roles in the living cells. They are commonly involved in a wide range of intermolecular interactions, and some of them possess remarkable binding promiscuity, being able to interact specifically with structur...
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PMID: 21440685
PDF is available here.
Abstract
We start by analyzing the compactness of the conformations thus sampled using their radius of gyration profiles. A more detailed analysis is then performed using dissimilarity measures, principal coordinate analysis, and free energy landscapes, with the aim of identifying groups of similar conformat...
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PMID: 21405018
PDF is available here.
Abstract
Heat shock protein 90 (Hsp90) is a significant target in the development of rational cancer therapy, due to its role at the crossroads of multiple signaling pathways associated with cell proliferation and viability. Here, a novel series of Hsp90 inhibitors containing a quinolein-2-...
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PMID: 21374821
PDF is available here.
Abstract
We use single-molecule force clamp spectroscopy (SMFCS) to explore the reactivity of tris(2-carboxyethyl)phosphine (TCEP), 1, 4-dl-dithiothreitol (DTT) and hydrosulfide anion (HS(-)) on disulfide bonds within a mechanically stretched polypeptide. The single-bond level bimolecular nucleophilic substit...
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PMID: 21341766
PDF is available here.
Abstract
We offer an alternative view that removes the need for sequence-context parameterization by focusing on individual microsopic interactions within a free energy decomposition and explicitly account for nonadditivity in conformational entropy through network rigidity using a Distance Constraint Model...
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PMID: 21280020
PDF is available here.
Abstract
Several neurodegenerative diseases share a common neuropathology, primarily featuring the presence of abnormal protein inclusions in the brain containing specific misfolded proteins. Strategies to decrease the load of protein aggregates and oligomers are considered relevant targets f...
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PMID: 21252621
PDF is available here.
Abstract
We use ΔN6, a truncation variant of the naturally amyloidogenic protein β(2)-microglobulin (β(2)m), to determine the solution structure of a nonnative amyloidogenic intermediate at high resolution. The structure of ΔN6 reveals a major repacking of the hydrophobic core to accommodate the nonnativ...
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PMID: 21255727
PDF is available here.
Abstract
Trimeric autotransporter adhesins (TAAs) are a family of secreted Gram-negative bacterial outer membrane (OM) proteins. These obligate homotrimeric proteins share a common molecular organisation, consisting of a N-terminal "passenger" domain followed by a C-terminal translocation unit/membrane anchor...
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PMID: 21557062
PDF is available here.
Abstract
Pyrazinamidase (PncA) activates the first-line antituberculous drug pyrazinamide into pyrazinoic acid. The crystal structure of the Mycobacterium tuberculosis PncA protein has been determined, showing significant differences in the substrate binding cavity when compared to the pyrazinamidases from Py...
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PMID: 21283666
PDF is available here.
Abstract
We describe two approaches within the Rosetta structure modeling methodology for treating such regions. The first does not require advance knowledge of the regions likely to be disordered; instead these are identified by minimizing a simple free energy function used previously to model protein foldi...
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PMID: 21829444
PDF is available here.
Abstract
We relax the latter assumption and explore how the bilayer junction responds to changes in this disjoining force using a simple one-dimensional energetic model, which reproduces key features of the bilayer regulation of gramicidin channel lifetimes....
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PMID: 21326605
PDF is available here.
Abstract
We determined its crystal structure. AtGPA1 is structurally similar to animal G protein α subunits, but our crystallographic and biophysical studies revealed that it had distinct properties. Notably, the helical domain of AtGPA1 displayed pronounced intrinsic disorder and a tendency to disengage fr...
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PMID: 21304159
PDF is available here.
Abstract
A growing number of research consortia are now focused on generating antibodies and recombinant antibody fragments that target the human proteome. A particularly valuable application for these binding molecules would be their use inside a living cell, e.g., for imaging or functional...
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PMID: 21099369
PDF is available here.
Abstract
We isolate and characterize the human protein named Rep8 or Ubxd6 as a new cofactor of p97. Mouse Rep8 is highly tissue-specific and abundant in gonads. In testes, Rep8 is expressed in post-meiotic round spermatids, whereas in ovaries Rep8 is expressed in granulosa cells. Rep8 associates directly wi...
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PMID: 21949850
PDF is available here.
Abstract
Proteins folding and unfolding are conformational changes in the life of the proteins, which reveal the modifications in the organization of the molecules inside the chain. It is known that a very organized structure has great amount of entropy and tends to exchange the energy with the environment. T...
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PMID: 21424091
PDF is available here.
Abstract
We have examined the biophysical properties of a recombinant murine amelogenin (rM180) and two point mutations identified from human DNA sequences in two cases of AI (T21I and P41T). At pH 5.8 and 25 °C, wild type (WT) rM180 and mutant P41T existed as monomers, and mutant T21I formed lower order ol...
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PMID: 20929860
PDF is available here.