Steps in the pathway of the thermal unfolding of ribonuclease A. A nonspecific photochemical surface-labeling study

Matheson, R. R.; Scheraga, Harold A.

doi:10.1021/bi00579a001

Cited by 51 publications

(39 citation statements)

References 44 publications

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“…Many of these residues are in regions of the protein that have been shown to be important for folding and protein stability. [79][80][81] Typically, residues in a hydrophobic core tolerate substitution with other non-polar residues but not with polar residues. 4-6 , 8,10,11,82 Most substitutions in the hydrophobic core that were identified with our selection system have a hydrophobic residue replaced with a polar or charged residue.…”

Section: Group II Residues (Buried Residues)mentioning

confidence: 99%

Genetic Selection for Critical Residues in Ribonucleases

Smith

Raines

2006

Journal of Molecular Biology

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Section: Group II Residues (Buried Residues)mentioning

confidence: 99%

Genetic Selection for Critical Residues in Ribonucleases

Smith

Raines

2006

Journal of Molecular Biology

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“…However, the occurrence of an intermediate, pretransitional state or sequential events has been characterized in many proteins [1][2][3]. Moreover, these noncooperative events occurring during thermal transition, which reflect the different local stabilities of the protein, have been associated with many important biological processes including folding, oligomerization or aggregation, enzyme activity, and function [4][5][6][7].…”

Section: Introductionmentioning

confidence: 99%

“…However, different regions were characterized to be responsible to the pretransitional state when different techniques were used. The pioneering work by Scheraga's group [1,24] proposed that the unfolding process was composed of at least three overlapping stages, and the first step (30-45ºC) consisted of unfolding of residues 13-25 and changing of residues 1-12. Using NMR techniques, Zhang et al [25] proposed that the first event in RNase A pressure unfolding was the change of the N-terminal helix I, which then moved away from the main structure of the RNase A.…”

Section: Introductionmentioning

confidence: 99%

Sequential Events in Ribonuclease A Thermal Unfolding Characterized by Two-Dimensional Infrared Correlation Spectroscopy

Zhang

He²,

Wang³

et al. 2006

PPL

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The conformational changes in the thermal denaturation of bovine pancreatic ribonuclease A was followed with infrared spectra and analyzed by second derivative and two-dimensional correlation techniques. By analyzing the sequential events in each transition stage, the results were consistent with a step-wise thermal denaturation mechanism in which the structural adjustment of the N-terminal and the opening of the central structure of the protein come before the main unfolding process. Non-native turns were found to form along with the unfolding of the native structures. The central region that is composed of some beta-sheet and alpha-helical structures was found to be the most stable part that might form the residual structure at high temperatures.

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“…This pathway was subsequently modified slightly (19,22) to take into account the results of photochemical surface labeling experiments (22) and of immunochemical studies (19). The modified pathway, derived from experimental data, is summarized in Table 2.…”

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confidence: 99%

A possible folding pathway of bovine pancreatic RNase.

Némethy¹,

Scheraga²

1979

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

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A theoretical pathway for the folding of RNase into its native conformation is derived from the contact map computed from crystallographic coordinates. The pathway is based on the hypothesis of Tanaka and Scheraga, according to which localized conformations stabilized by short-and medium-range interactions form before those conformational features that are stabilize primarily by long-range interactions. The pathway deduced from the contact map agrees with experimental information on intermediates detected in the thermal unfolding of RNase and in immunochemical studies on the formation of stable antigenic sites when reduced RNase is oxidized with glutathione. Ambiguities in the interpretation of the contact map are resolved by the combination of structural information contained in the cotitact map and experimental information.Contact maps (1)(2)(3)(4)(5) [and related, more quantitative representations, distance maps (6-10)] have been used to analyze the structures of native proteins (2,(6)(7)(8) and to compare the results of simulations of protein folding to the native structure (1, 3-5, 9). Some studies have dealt with the description of ordered structures, such as a-helices and parallel or antiparallel pleated sheets on the contact map (7,8) or with the recognition of large structural domains (2, 10). Although most of these studies concerned the native structure, we recently exploited the results of Monte Carlo calculations (1) and introduced a hypothetical mechanism of protein folding, based on a qualitative visual analysis of contact maps (2). It was shown that a self-consistent pathway of folding can be postulated for several proteins on the basis of the contact map alone.In this communication, we show that the pathway for the folding of RNase, derived from the contact map, is consistent with the one proposed on the basis of experimental information on intermediates during both thermal unfolding (with intact disulfide bonds) and glutathione oxidation of the reduced protein. Theoretical analysis and the interpretation of experimental data complement each other by narrowing the possible choices of pathways. Experimental data on the unfolding of RNase and the arguments that support the concept of a preferred pathway have been reviewed elsewhere (11-13). METHODSThe contact map shown in Fig. 1 (Fig. 1) Fig. 1 by using the hypothesis of Tanaka and Scheraga (2). This hypothesis assumes that short-range interactions take precedence over mediumrange interactions, and medium-range interactions take precedence over long-range interactions. This criterion is satisfied by pathways in which contacts near the diagonal of the contact map are formed first, and contact regions are then formed in the order of increasing distance from the diagonal. The contact regions can be ordered by using the point with the smallest values of Ii -j

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Steps in the pathway of the thermal unfolding of ribonuclease A. A nonspecific photochemical surface-labeling study

Cited by 51 publications

References 44 publications

Genetic Selection for Critical Residues in Ribonucleases

Genetic Selection for Critical Residues in Ribonucleases

Sequential Events in Ribonuclease A Thermal Unfolding Characterized by Two-Dimensional Infrared Correlation Spectroscopy

A possible folding pathway of bovine pancreatic RNase.

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