Ensemble modulation as an origin of denaturant-independent hydrogen exchange in proteins 1 1Edited by I. Wilson

Wooll, John O.; Wrabl, James O.; Hilser, Vincent J.

doi:10.1006/jmbi.2000.3889

Cited by 40 publications

(45 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The physical model for three state denaturation in nuclease is that the C-terminal helix, which ends with tryptophan 140, unfolds in the first transition. Carra and Privalov propose that the other helices unfold in this transition as well, leaving only the beta barrel structure, an idea supported by some hydrogen exchange data [16,19,20]. The remaining structure then breaks down cooperatively in a subsequent step.…”

Section: Introductionmentioning

confidence: 75%

Thermal denaturations of staphylococcal nuclease wild-type and mutants monitored by fluorescence and circular dichroism are similar: Lack of evidence for other than a two state thermal denaturation

Byrne

Stites

2007

Biophysical Chemistry

View full text Add to dashboard Cite

It is unclear whether the thermal denaturation of staphylococcal nuclease is a two state, three state, or variable two state process. The thermal denaturation of wild-type staphylococcal nuclease was followed by tryptophan fluorescence and circular dichroism signal at 222 nm, forty-two and fourteen times respectively. Analysis of this data using a simple two state model gave melting temperatures of 53.0 ± 0.4°C (fluorescence) and 52.7 ± 0.6°C (CD) and van't Hoff enthalpies of 82.4 ± 2.6 kcal/ mol and 88.6 ± 4.2 kcal/mol. Ninety-seven mutants also had these parameters determined by both fluorescence and CD. The average difference between the melting temperatures was 1.05 ± 0.75°a nd the average difference between van't Hoff enthalpies was 1.6 ± 4.8 kcal/mol. These very similar results for the two spectroscopic probes of structure are discussed in the context of the different models that have been proposed for nuclease denaturation. It is concluded, for most nuclease variants, that the errors introduced by a two state assumption are negligible and either virtually all helical structure is lost in any initial unfolding event or any intermediate must have low stability.

show abstract

Section: Introductionmentioning

confidence: 75%

Thermal denaturations of staphylococcal nuclease wild-type and mutants monitored by fluorescence and circular dichroism are similar: Lack of evidence for other than a two state thermal denaturation

Byrne

Stites

2007

Biophysical Chemistry

View full text Add to dashboard Cite

show abstract

“…17,20,22 Others have used solvent accessibility. 18,21,47 We find that even H-bonding to a water molecule does not always correspond to HX competence, 43 which ultimately depends on the ability to form an H-bond to HX catalyst, typically the solvent hydroxide ion.…”

Section: Structural Dynamicsmentioning

confidence: 85%

“…[12][13][14][15] For more buried hydrogens, predictions of HX rates based on local interaction density and the calculation of structural dynamics have been attempted. [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34] We compare these models to SN HX data and discuss the problematic issues.…”

Section: Introductionmentioning

confidence: 99%

Protein hydrogen exchange: Testing current models

et al. 2012

View full text Add to dashboard Cite

To investigate the determinants of protein hydrogen exchange (HX), HX rates of most of the backbone amide hydrogens of Staphylococcal nuclease were measured by NMR methods. A modified analysis was used to improve accuracy for the faster hydrogens. HX rates of both near surface and well buried hydrogens are spread over more than 7 orders of magnitude. These results were compared with previous hypotheses for HX rate determination. Contrary to a common assumption, proximity to the surface of the native protein does not usually produce fast exchange. The slow HX rates for unprotected surface hydrogens are not well explained by local electrostatic field. The ability of buried hydrogens to exchange is not explained by a solvent penetration mechanism. The exchange rates of structurally protected hydrogens are not well predicted by algorithms that depend only on local interactions or only on transient unfolding reactions. These observations identify some of the present difficulties of HX rate prediction and suggest the need for returning to a detailed hydrogen by hydrogen analysis to examine the bases of structure-rate relationships, as described in the companion paper (Skinner et al., Protein Sci 2012;21:996-1005).

show abstract

“…Although, the exact mechanism of denaturant-independent exchange is unclear, previous studies have proposed a "local structural fluctuation" (56) model, which posits a transient opening of the exchanging residues one at a time without significant surface area exposure. Alternatively, a statisticalmechanical approach proposes denaturant-induced modulation of populations of exchange-competent (open) and exchange-incompetent (closed) states to result in no net change in ⌬G op with a change in denaturant concentration (57). Residues in the loops are expected to exchange fast as loops are flexible and lack any ordered structure.…”

Section: Discussionmentioning

confidence: 99%

Partially Unfolded Forms of the Prion Protein Populated under Misfolding-promoting Conditions

Moulick

Das

Udgaonkar

2015

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background: Folding intermediates of proteins are known to initiate misfolding. Results: Two partially unfolded forms (PUFs) of the prion protein have been characterized structurally and energetically. Conclusion: One of the PUFs is structurally similar to an initial intermediate in prion misfolding. Significance: Identification of aggregation-prone intermediates on the prion protein's folding pathway is the key to understanding its amyloidogenic propensity.

show abstract

Ensemble modulation as an origin of denaturant-independent hydrogen exchange in proteins 1 1Edited by I. Wilson

Cited by 40 publications

References 33 publications

Thermal denaturations of staphylococcal nuclease wild-type and mutants monitored by fluorescence and circular dichroism are similar: Lack of evidence for other than a two state thermal denaturation

Thermal denaturations of staphylococcal nuclease wild-type and mutants monitored by fluorescence and circular dichroism are similar: Lack of evidence for other than a two state thermal denaturation

Protein hydrogen exchange: Testing current models

Partially Unfolded Forms of the Prion Protein Populated under Misfolding-promoting Conditions

Contact Info

Product

Resources

About