Secondary structure predictions and medium range interactions

Williams, Robert W.; Chang, Albert Y.; Juretić, Davor; Loughran, Sheila

doi:10.1016/0167-4838(87)90109-9

Cited by 160 publications

(191 citation statements)

References 15 publications

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“…Collectively this implies that the extra stability afforded to the first transition state for cFos-JunW E23K is compensated by the additional Q21R mutation in cFos-JunW Ph1 . The mutation does not cause any significant change in the helical propensity (1.27 versus 1.21 (36)), but rather appears to generate a better intermolecular partner for g2 Glu of c-Fos, by giving a favorable chargecharge interaction (see Fig. 1).…”

Section: Resultsmentioning

confidence: 99%

“…The mutation of Glu to Lys at position gЈ3 (see Fig. 1) is predicted to be of slightly lower helical propensity (1.59 versus 1.23) according to an experimental study on coiled coil systems that accounts for both solventexposed and buried residues, as well as residues located at the center of the helix and at the termini (36). Pairing with Leu at position e4 of c-Fos (for notation see Fig.…”

Section: Resultsmentioning

confidence: 99%

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Improved Stability of the Jun-Fos Activator Protein-1 Coiled Coil Motif

Mason

Hagemann

Arndt

2007

Journal of Biological Chemistry

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The second phase is independent of concentration and is exponential. In contrast, in the unfolding direction, all molecules display two-state kinetics. Collectively this implies a transition state between unfolded helices and dimeric intermediate that is readily traversed in both directions. We demonstrate that the added stability of cFos-JunW Ph1 relative to cFos-JunW is achieved via a combination of kinetic rate changes; cFosJunW E23K has an increased initial dimerization rate, prior to the major transition state barrier while cFos-JunW Q21R displays a decreased unfolding rate. The former implies that improved hydrophobic burial and helix-stabilizing mutations exert their effect on the initial, rapid, monomer-collision event. In contrast, electrostatic interactions exert their effect late in the folding pathway. Although our focus is the leucine zipper region of the oncogenic transcription factor Activator Protein-1, coiled coils are ubiquitous and highly specific in their recognition of partners. Consequently, generating kinetic-based rules to predict and engineer their stability is of major significance in peptidebased drug design and nano-biotechnology.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Improved Stability of the Jun-Fos Activator Protein-1 Coiled Coil Motif

Mason

Hagemann

Arndt

2007

Journal of Biological Chemistry

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“…It is interesting to compare the information measures with results obtained investigating residue a-helix propensities (Bryson et al, 1995), both previous statistical work (e.g., Gibrat et al, 1987;Williams et al, 1987), and the larger literature based on direct experimentation, e.g., using directed mutagenesis (Horovitz et al, 1992;Blaber et al, 1993) and model peptides (Padmanabhan et al, 1990). The correlation of the DSC intraresidue information for the 20 residues with a-helix propensities of the other methods is: Gibrat et al (1987) surveys has the advantage over physical-based methods in being based on many more proteins, and thus averaged over all types of protein environment.…”

Section: Discussionmentioning

confidence: 99%

Identification and application of the concepts important for accurate and reliable protein secondary structure prediction

1996

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A protein secondary structure prediction method from multiply aligned homologous sequences is presented with an overall per residue three-state accuracy of 70.1 %. There are two aims: to obtain high accuracy by identification of a set of concepts important for prediction followed by use of linear statistics; and to provide insight into the folding process. The important concepts in secondary structure prediction are identified as: residue conformational propensities, sequence edge effects, moments of hydrophobicity, position of insertions and deletions in aligned homologous sequence, moments of conservation, auto-correlation, residue ratios, secondary structure feedback effects, and filtering. Explicit use of edge effects, moments of conservation, and auto-correlation are new to this paper. The relative importance of the concepts used in prediction was analyzed by stepwise addition of information and examination of weights in the discrimination function. The simple and explicit structure of the prediction allows the method to be reimplemented easily. The accuracy of a prediction is predictable a priori. This permits evaluation of the utility of the prediction: 10% of the chains predicted were identified correctly as having a mean accuracy of >80%. Existing high-accuracy prediction methods are "black-box" predictors based on complex nonlinear statistics (e.g., neural networks in PHD: Rost & Sander, 1993a). For medium-to short-length chains ( 2 9 0 residues and

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“…Consistently, Ala 24 located on The relative hydrophobicities were taken from the consensus hydrophobicity scale of Eisenberg (24). P␣, P␤, and Pt represent the normalized frequencies for each conformation (25). the opposite site of the helical wheel of h͞rCRF was found to be not important for binding to CRFBP.…”

Section: Discussionmentioning

confidence: 99%

A single amino acid serves as an affinity switch between the receptor and the binding protein of corticotropin-releasing factor: Implications for the design of agonists and antagonists

Eckart

Jahn

Radulovic

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

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In view of the observation that corticotropin-releasing factor (CRF) affects several brain functions through at least two subtypes of G protein-dependent receptors and a binding protein (CRFBP), we have developed synthetic strategies to provide enhanced binding specificity. Human͞rat CRF (h͞rCRF) and the CRF-like peptide sauvagine (Svg), differing in their affinities to CRFBP by two orders of magnitude, were used to identify the residues determining binding to CRFBP. By amino acid exchanges, it was found that Ala 22 of h͞rCRF was responsible for this peptide's high affinity to CRFBP, whereas Glu 21 located in the equivalent position of Svg prevented high affinity binding to CRFBP. Accordingly, [Glu 22 ]h͞rCRF was not bound with high affinity to CRFBP in contrast to [Ala 21 ]Svg, which exhibited such high affinity. Furthermore, the affinity of both peptides to either CRF receptor (CRFR) subtype was not reduced by these replacements, and their subtype preference was not changed. Thus, exchange of Ala and Glu and vice versa in positions 22 and 21 of h͞rCRF and Svg, respectively, serves as a switch discriminating between CRFBP and CRFR. On the basis of this switch function, development of new specific CRF agonists and antagonists is expected to be facilitated. One application was the modification of the CRF antagonist astressin (Ast), whose employment in animal experiments is limited by its low solubility in cerebrospinal fluid. Introduction of Glu residues into Ast generated with [Glu 11,16 ]Ast an acidic astressin, which efficiently antagonized in vivo the CRFR1-dependent reduction of locomotion induced by ovine CRF without detectable binding to CRFBP.

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Secondary structure predictions and medium range interactions

Cited by 160 publications

References 15 publications

Improved Stability of the Jun-Fos Activator Protein-1 Coiled Coil Motif

Improved Stability of the Jun-Fos Activator Protein-1 Coiled Coil Motif

Identification and application of the concepts important for accurate and reliable protein secondary structure prediction

A single amino acid serves as an affinity switch between the receptor and the binding protein of corticotropin-releasing factor: Implications for the design of agonists and antagonists

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