protein folding

..Studies of other CFTR folding mutants and of conformational mutants in other protein folding diseases will examine the generality of Hsp27- SUMO mediated stabilization/degradation...

..Pyrrhocoricin, drosocin and perhaps apidaecin appear to inhibit chaperone-assisted protein folding via binding to the multihelical lid region of the 70 kDa heat shock protein DnaK with their amino terminal ..

..suspect that the brain disease induced by FrCasE and related murine retroviruses represents a virus-induced protein folding disease...

In the past decade, protein folding has gained wider recognition and acceptance as an important field of biomedical research due, in part, to the growing number of examples of protein misfolding that have been linked to human diseases...

..precursors of Entamoeba and Trichomonas are sufficient for N- glycan-dependent quality control (QC) of protein folding, N-glycan-dependent QC is absent from Giardia and Plasmodium...

..binding to the multihelical lid region of the 70 kDa heat shock protein DnaK and inhibit chaperone-assisted protein folding. Pyrrhocoricin and its designed analogs kill (-lactam-, tetracycline- and aminoglycoside-resistant ..

..Unlike mammalian amyloid fibers that appear to be formed by aberrant pathways of protein folding, curli assembly in bacteria involves a dedicated multistep pathway that requires the csgBA and csgDEFG ..

..We also have been studying protein folding intermediates by fluorescence to determine intramolecular distances in order to compare these with the native ..

..A major goal is the determination of a parameter that is fundamental to understanding the nature of protein folding: the speed with which the different unfolded conformations interconvert with one another...

..We study the close relationship between protein folding and packaging into ER- derived COPII vesicles in the model organism, Saccharomyces cerevisiae...

..We study the close relationship between protein folding and packaging into ER- derived COPII vesicles in the model organism, Saccharomyces cerevisiae...

..On a larger scale, electrostatic interactions affect protein folding, macromolecular interactions and the assembly of subunits into larger structures...

..Molecular chaperones play key roles in muscle development and function by aiding protein folding and inhibiting protein denaturation and aggregation...

..recent research has been focused on molecular chaperones, the cellular machinery responsible for maintaining protein folding or mediating the degradation of irreparably damaged proteins...

..important role in such biologically important process as transport across membranes, protein degradation and protein folding. It is the long-term goal of this work to elucidate the thermodynamic properties of the denatured ensemble, ..

..However, relatively little is known about the nature of their contribution to protein folding and stability...

..By conducting these experiments at different temperatures, heat capacity information will be obtained...

..in the setting of a specific P-gp haplotype can affect efficiency of P-gp pumping by altering the rhythm of protein folding and changing substrate and inhibitor interactions with P-gp...

..In the cell, protein folding into its native structure is assisted by enzymes that accelerate folding and by chaperones that inhibit ..

..suggests that N-glycans (attached to the amide nitrogen of an Asn side-chain) play crucial roles in mediating protein folding and secretion by directly increasing protein folding rates and stability...

..In the cell, protein folding into its native structure is assisted by enzymes that accelerate folding and by chaperones that inhibit ..

..The primary objective of this proposed work is the development of fundamental links between the nature of the protein folding free energy landscape and the underlying mechanism and kinetics of protein folding...

..The protein folding environment in the ER is regulated by signal transduction pathways that together constitute the ER unfolded ..

..Molecular chaperones, in addition to catalyzing protein folding and translocation, play several essential functions in this degradative process, which we hope to understand...

..Molecular chaperones, in addition to catalyzing protein folding and translocation, play several essential functions in this degradative process, which we hope to understand...

..Initially, Hsps were demonstrated to play an important role in protein folding and chaperoning...

..of the LS domain such as proposed polarizability is important not only for fuller understanding of protein folding or protein engineering but also for understanding physiological as well as pathological cellular processes ..

..surface or for the external milieu are first translocated into the endoplasmic reticulum (ER) where initial protein folding and modifications occur that are essential for the protein to attain its appropriate functional conformation ..

..growth, development and in the protection against diseases that include cancer, cardiovascular disease and protein folding diseases such as Alzheimer's Huntington's and prion-based disease...

..at perturbing and/or reversing the equilibrium between conformations in diseases associated with abnormal protein folding. In recent years, Saccharomyces cerevisiae has emerged as an experimentally tractable model system for the ..

..at perturbing and/or reversing the equilibrium between conformations in diseases associated with abnormal protein folding. In recent years, Saccharomyces cerevisiae has emerged as an experimentally tractable model system for the ..

..to support the 2006 Federation of American Society of Experimental Biologists (FASEB) Summer Conference on "Protein Folding in the Cell" to be held July 29 to August 3, 2006 in Saxtons River, VT...

..coli. We will exploit the recent discovery that lipids in E. coli cells assist membrane protein folding by specific interactions with folding intermediates in a manner analogous to protein molecular chaperones...

DESCRIPTION (application abstract): The chaperonin TRiC is a protein folding nanomachine necessary for the growth of all eukaryotic cells...

DESCRIPTION (application abstract): The chaperonin TRiC is a protein folding nanomachine necessary for the growth of all eukaryotic cells...

DESCRIPTION (provided by applicant): Intracellular chaperones not only regulate protein folding but are also key mediators of the degradation and disposal of misfolded and damaged proteins...

..The UPR is a feedback pathway by which cells regulates the levels of proteins involved in secretory pathway protein folding by inducing transcription of their genes in response to detected shortfalls in their levels...

..predictions helps uncover function and cellular activity and is also of general interest as an analog of the protein folding problem...

..Transgenic H-2Kb expression overwhelms the protein folding system of muscle fibers and activates an UPR, which appears to mimic what occurs in human myositis...

..Besides its key functions in enzyme catalysis and protein folding and stability, Zn2+ plays major roles in normal development and growth, in cancer, in immune response, in ..

..CD and NMR are the most widely used techniques for studying protein folding and conformational transitions in DNA and RNA...

..CD and NMR are the most widely used techniques for studying protein folding and conformational transitions in DNA and RNA...

The physical basis of protein folding defines a second "genetic code". Interest in mechanisms of folding has recently been stimulated by the discovery of human diseases caused by the misfolding and aggregation of diverse proteins...

..Transgenic H-2Kb expression overwhelms the protein folding system of muscle fibers and activates an UPR, which appears to mimic what occurs in human myositis...

..that these conformational transitions and polypeptide-binding properties are important for calreticulin's protein folding and cross-priming functions in cells...

DESCRIPTION (provided by applicant): Protein folding abnormalities resulting from mutations in the coding regions of many genes represent the molecular basis for a large number of disease states...

..that these conformational transitions and polypeptide-binding properties are important for calreticulin's protein folding and cross-priming functions in cells...

..folding substrates, we propose experiments intended to uncover general principles for chaperone-dependent protein folding. In order to study the dynamics of the GroEL chaperonin and how it interacts with protein folding ..

..Arimoclomol, a co-inducer of heat shock protein gene expression, promotes de novo protein folding, facilitates repair of misfolded proteins and targets misfolded proteins for degradation...

..Many loss-of-function human genetic diseases result from mutations that cause delayed protein folding kinetics rather than generating terminally misfolded polypeptides...

..folding energetics and contrasting them with misfolding energetics is essential for understanding the role of protein folding in health and disease, and for designing backbone modified proteins with enhanced physical properties...

..Unlike the "protein folding problem" which has been under study for many decades, the study of RNA tertiary structure stability and ..

The objective of this proposal is to study protein folding using single-molecule fluorescence methodology. Understanding protein folding is fundamental to deciphering how the genetic code is translated into functional protein units...

..a general framework with which to pharmacologically manipulate physiological and pathological parameters of protein folding disorders...

..Probe early events (starting on the us time scale) during the formation -of native azurin, flavodoxin and cytochrome...

DESCRIPTION (provided by applicant): The major difficulty in deciphering the protein folding code is that folding information is diffuse...

..the incidence of further aggregation to a protein precipitate? Further elucidation of the mechanisms of protein folding/oligomerization is required to understand the basic mechanisms of illnesses such as Alzheimer's Disease, ..

..folding energetics and contrasting them with misfolding energetics is essential for understanding the role of protein folding in health and disease, and for designing backbone modified proteins with enhanced physical properties...

..Many loss-of-function human genetic diseases result from mutations that cause delayed protein folding kinetics rather than generating terminally misfolded polypeptides...

..e., theranostics)...

..roles in cells of all living organisms through their action in many aspects of protein metabolism, including protein folding, cellular growth control, neurotransmission, steroid receptor maturation, tumor suppression, and oncogenesis...

..Our third aim is to streamline the purification process for GroEL so that the costs of the protein which are currently very high, will not limit the usefulness of the system to the research community...

Classical protein folding invokes a cooperative transition between distinct thermodynamic states that are individually populated at equilibrium and separated by an energy barrier...

..From this analysis, we predict that correlated mutations that reduce the frustration in the second half of helix 2 in mammalian prion proteins could inhibit the formation of PrP(Sc)...

..We find that alpha/beta proteins with alternating alpha and beta segments (such as the beta-barrel) are more stable than proteins in other fold classes...

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..2 angstroms) to the design model. The ability to design a new protein fold makes possible the exploration of the large regions of the protein universe not yet observed in nature...

..The redesigned enzyme induced an increased, temperature-dependent bacterial growth rate under conditions that required its activity, thereby coupling molecular and metabolic engineering...

..These predictions were subsequently validated by NMR and CD experiments...

..Overall, a practical high-throughput approach for de novo protein design has been developed that may have fruitful application for any type of tertiary structure...

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..The structure explains the molecular basis of a low severity form of lissencephaly...

..The rigid central beta-strand domain is surrounded by the peripheral alpha-helical and coil structures, which are marginally stable toward a chemical denaturant...

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..These could enable us to identify the downhill folding or the cooperative two-state folding behavior solely from the native structures of proteins...

Search and study of the general principles that govern kinetics and thermodynamics of protein folding generate a new insight into the factors controlling this process...

..Further studies point to the correlation between stability of full-length CAP with its multimerisation behaviour, where oligomer formation leads to a more stable protein...

..The symmetric self-association between two identical mis-translated CFr sub-domains to generate an extremely stable structure parallels a mechanism for natural protein-fold evolution by modular recombination of protein sub-structures...

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..This stretch, which may be only structured transiently in the isolated molecule, could play a major role in Grb14 PIR binding to a biological partner by undergoing a structural transition...

..These results provide a basis for further structural investigations that could be used for the rational design of potential agonists and antagonists essential in human therapy...

..The 1H/2H exchange experiments showed that the protection factors of a mixture of the native and cold-denatured states is strongly biased by that of the labile cold-denatured state, consistent with a two-process model of the exchange...

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..sensor Ire1 to trigger the unfolded protein response (UPR), a homeostatic signaling pathway that adjusts ER protein folding capacity according to need...

..In addition, the subunit fusion strategy described in this study can be used, where applicable, to modify oligomeric proteins in general...

..Knowledge of the protease monomer structure and critical features of its dimerization may aid in the screening and design of compounds that target the protease prior to its maturation from the Gag-Pol precursor...

..Kinetic studies with single amino acid mutants in helix A indicate that it modulates the affinity of APRin for APR primarily by influencing the dissociation rate of the inhibitor from the complex...

..We discuss these results in relation to a hierarchical pathway of protein folding and misfolding. The Ala(A2) analog's low biological activity (0...

..Ala-14 provides a high-resolution portrait of the unfolded state and the process of helix nucleation and propagation in the absence of tertiary contacts, information that bears on early events in protein folding.

..The comparatively compact shapes of the denatured and apo forms may explain, in part, the marginal stability of the native fold...

..It is more consistent with modest contributions from many H+ binding groups, with an important role for local conformational fluctuations in the coupling between H+ binding and the global structural transition...

..The oligomerization mode observed in the crystal structure of 132-236 may not exist in the intact repressor bound to the operator since it is shown to contradict several published biochemical data on the intact repressor...

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..These studies emphasize an unexpected role for Ub's core in molecular recognition and suggest that the diversity of protein-protein interactions in which Ub engages placed enormous constraints on its evolvability...

..In conclusion, the structure of OmlA does suggest that this protein may be implicated in protein-protein interactions required during X. citri infection...

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..4 kcal mol(-1), is consistent with the presumption that the >45 kcal (mol trimer)(-1) generated by the binding of three ions represents the major contribution to the stability of the holo-trimeric Cam...

..Inhibitor or substrate binding to these mutants compensates for the lack of long-range interactions generated by W140...

..Structural and biochemical analysis implies that Mtb DsbE functions differently from Gram-negative DsbE homologs, and we discuss its possible functional role in the bacterium...

..The calculated melting temperature of GB1 agrees with early experiment. The results also agree with the recent experiment result in which GB1 has more than one intermediate...

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..Furthermore, the implications of this in vitro refolding study on the in vivo folding process of HPI have been discussed...

..It identifies a number of potentially stabilizing ionic interactions including a cation-binding site and reveals significant changes in the electrostatic surface potential...

..Combining biophysical, mass-spectrometry data and molecular model is a useful strategy to obtain structural information and to help in prioritizing targets in structural genomics programs...

..3-fold reduction in affinity for ATP. The C1104F mutation significantly alters protein folding, whereas C1104A does not affect the structure or function of the N-domain...

..We conclude that the BtuB binding sites for cobalamins and enzymatic E-colicins are overlapping but inequivalent and that the distal loop and (possibly) the short alpha-helical flanking regions are sufficient for high affinity binding...

..These results demonstrate the success of combining kinetic and equilibrium simulations of minimalist protein models to explore TIM barrel folding and the folding of other large proteins...

..Our simulations also predicted the presence of a nucleation site, onto which several hydrophobic residues condensed forming the foundation for the central betaalphabetaalphabeta module...

..Our simulation has provided important detailed structural information about the partially unfolded state of TTR that may be related to the amyloidogenic intermediates...

Molecular chaperones assist protein folding by facilitating their "forward" folding and preventing aggregation. However, once aggregates have formed, these chaperones cannot facilitate protein disaggregation...

..The dynamic behavior of these alpha-helices induced by increased kinetic energy during the unfolding process is considered to be similar to the expansion and compression of a series of springs under the influence of mechanical stress...

..Moreover, the flexibility might be essential in sustaining the allosteric properties of the enzyme bound in the complex...

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..Conversely, the excessive stablization of the local secondary structure elements, which are rarely detected in the TSE, has a detrimental effect on convergence to the native bound structure...

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