Measuring the Conformational Stability of a Protein by Hydrogen Exchange
Humana Press eBooksPublished 15 November 2003
Beatrice M.P. Huyghues‐Despointes, C. Nick Pace, S. W. Englander, J. Martin Scholtz
Citations78
Generate an AI Snapshot to get a quick, structured summary of this paper.
Study Snapshot
ObjectiveStudy objective
MethodsResearch methodology
PopulationPopulation studied
Sample sizeSample sizes
OutcomesStudy outcomes here
ResultsStudy results comes here
LimitationsResearch study limitations comes here
A concise AI-generated summary of the paper will appear here once you click Generate AI Snapshot.
Abstract
Measuring the conformational stability of a protein is one key to solving the protein folding problem. It is also of practical importance for answering questions such as these:
Keywords
ChemistryMaterials ScienceBiochemistry, Genetics and Molecular Biology
The Journal of Physical ChemistryUSE OF GLASS ELECTRODES TO MEASURE ACIDITIES IN DEUTERIUM OXIDE<sup>1,2</sup>
2,161 Citations1960Paul K. Glasoe, F. A. Long
Proteins Structure Function and BioinformaticsPrimary structure effects on peptide group hydrogen exchange
1,922 Citations1993Yawen Bai, John Milne +2 more
The results provide the information necessary to evaluate measured protein NH to ND exchange rates by comparing them with rates to be expected for the same amino acid sequence is unstructured aligo‐ and polypeptides.
Advances in protein chemistryHydrogen Exchange in Proteins
1,132 Citations1966Aase Hvidt, Sigurd O. Nielsen
Quantitative measurements of the rate of hydrogen exchange in a given protein, under specified experimental conditions, provide a multiparameter characterization of the protein conformation (or distribution of conformations) present under these conditions.
BiochemistryConsideration of the possibility that the slow step in protein denaturation reactions is due to cis-trans isomerism of proline residues
1,113 Citations1975John F. Brandts, Herbert R. Halvorson +1 more
Since the present model assumes that only one of the major kinetic phases seen in denaturation reactions is concerned with the denaturation process per se, it is in agreement with numerous thermodynamic studies which show consistency with the two-state model for unfolding.
ScienceProtein Folding Intermediates: Native-State Hydrogen Exchange
999 Citations1995Yawen Bai, Tobin R. Sosnick +2 more
The partially unfolded forms detected by hydrogen exchange appear to represent the major intermediates in the reversible, dynamic unfolding reactions that occur even at native conditions and thus may define the major pathway for cytochrome c folding.
Progress in Biophysics and Molecular BiologyFolding and association of proteins
692 Citations1987Rainer Jaenicke
For small proteins successive stages in the folding have been resolved kinetically; these suggest that H-bonded elements of secondary structure are formed first, followed by folding steps to generate the complete tertiary structure.
The FASEB JournalForces contributing to the conformational stability of proteins
658 Citations1996C. Nick Pace, Bret A. Shirley +2 more
It is suggested that hydrogen bonding and the hydrophobic effect make large but comparable contributions to the stability of globular proteins.
CRC Critical Reviews in BiochemistryThe Stability of Globular Protein
652 Citations1975C. Nick Pace, Jan Hermans
BiochemistryPrimary structure effects on peptide group hydrogen exchange
471 Citations1972Robert S. Molday, S. W. Englander +1 more
The results provide the information necessary to evaluate measured protein NH to ND exchange rates by comparing them with rates to be expected for the same amino acid sequence is unstructured oligo- and polypeptides.
Journal of Molecular BiologySide-chain effects on peptidyl-prolyl cis/trans isomerisation
353 Citations1998Ulf Reimer, Gerd Scherer +4 more
There is a rough correlation between the cis content in the oligopeptides and the propensity of Xaa-Pro cis prolyl bonds in proteins, which suggests that the prolyL bond conformation is mainly determined by local effects in proteins.
BiochemistrypH dependence of the urea and guanidine hydrochloride denaturation of ribonuclease A and ribonuclease T1
331 Citations1990C. Nick Pace, Douglas V. Laurents +1 more
The unfolded states of proteins in urea and GdnHCl solutions may differ significantly in the extent of their interaction with denaturants, suggesting that the conformations assumed by unfolded proteins may depend to at least some extent on the amino acid sequence of the protein.
Nature Structural & Molecular BiologyDetection of rare partially folded molecules in equilibrium with the native conformation of RNaseH
321 Citations1996Aaron K. Chamberlain, Tracy M. Handel +1 more
Data suggest that the first region to fold is the thermodynamically most stable portion of the protein and that the molten globule is a high free energy conformation present at equilibrium in the native state.
Journal of Molecular BiologyNon-proline Cis peptide bonds in proteins
314 Citations1999Andreas Jabs, M.S. Weiss +1 more
On the basis of the experience with the structure determination of coagulation factor XIII, an algorithm is developed for the identification of possibly overlooked cis peptide bonds that exploits the deviations of geometrical parameters from ideality.
Proteins Structure Function and BioinformaticsProtein stability parameters measured by hydrogen exchange
311 Citations1994Yawen Bai, John Milne +2 more
The hydrogen exchange (HX) rates of the slowest peptide group NH hydrogens in oxidized cytochrome c (equine) are controlled by the transient global unfolding equilibrium and can be measured by one‐dimensional nuclear magnetic resonance and used to determine the thermodynamic parameters of global unfolding at mild solution conditions well below the melting transition.
Nature Structural BiologySolvent isotope effect and protein stability
197 Citations1995George I. Makhatadze, G. Marius Clore +1 more
Analysis of thermodynamic data for the transfer of model compounds from H2O to D2O shows that almost all the changes in the enthalpy of unfolding and in the protein-ligand interactions due to water isotopic substitution can be rationalized by changes in hydration of the buried non-polar groups.
BiochemistryFolding Dynamics of the src SH3 Domain
191 Citations1997Viara Grantcharova, David Baker
Comparison of the src SH3 with homologous SH3 domains as well as with other small well-characterized beta-sheet proteins provides insights into the determinants of folding kinetics and protein stability.
The Journal of Physical Chemistry BThermodynamics of Protein Interactions with Urea and Guanidinium Hydrochloride
188 Citations1999George I. Makhatadze
ScienceGuanidinium Chloride Induction of Partial Unfolding in Amide Proton Exchange in RNase A
181 Citations1993Stephen L. Mayo, Robert L. Baldwin
The results indicate that these concentrations of GdmCl do induce exchange by means of a partial unfolding mechanism for all 23 protons; this implies that exchange reactions can be used to study the unfolding and stability of local regions.
Nature Structural BiologyProtein conformational stabilities can be determined from hydrogen exchange rates.
161 Citations1999J. Martin Scholtz, C. Nick Pace +1 more
Measuring protein conformational stability is one key to solving the protein folding problem and traditional methods are solvent or thermal denaturation.
BiochemistryAmide proton exchange in proteins by EX1 kinetics: studies of the basic pancreatic trypsin inhibitor at variable p2H and temperature
130 Citations1985Heinrich Röder, Gerhard Wagner +1 more
It can be concluded that the amide proton exchange in globular proteins is quite generally via EX2 processes, with rare exceptions for measurements with extremely stable protons at high temperature and basic p2H.
Current Opinion in Structural BiologyHydrogen exchange and protein folding
120 Citations1998Jane Clarke, Laura S. Itzhaki
Amide hydrogen-deuterium exchange is a sensitive probe of the structure, stability and dynamics of proteins and recent technical advances enable the methodology to be applied to the study of protein-protein interactions in much larger, more complex systems.
BiochemistryLocal Stability and Dynamics of Apocytochrome <i>b</i><sub>562</sub> Examined by the Dependence of Hydrogen Exchange on Hydrostatic Pressure<sup>,</sup>
110 Citations1998Ernesto J. Fuentes, A. Joshua Wand
The protein is found to have three regions of subglobal cooperative stability, and one of the subglobal unfolding units shows a significant positive volume change at low pressures suggesting the presence of a highly mispacked open state at ambient pressure.
Methods in enzymology on CD-ROM/Methods in enzymology[6] Thermal denaturation methods in the study of protein folding
108 Citations1995Ernesto Freire
The chapter discusses analysis of the heat capacity of proteins in different conformational states and its relation to structural parameters.
Nature Structural BiologyThe energetics of T4 lysozyme reveal a hierarchy of conformations.
107 Citations1999Susan Marqusee, Manuel Llinás +2 more
The overall subdomain hierarchy of energies does not mirror data on the folding pathway for this protein, challenging the relationship between energy landscapes and folding trajectories.
BiochemistryTemperature and pH Dependences of Hydrogen Exchange and Global Stability for Ovomucoid Third Domain
82 Citations1996Liskin Swint‐Kruse, Andrew D. Robertson
Results suggest that EX2 kinetics should not be assumed when interpreting exchange studies, and a subset of 6-11 residues exhibits a one-to-one correlation with global stability in turkey ovomucoid third domain.
BiochemistryLocal Dynamics and Stability of Apocytochrome <i>b</i><sub>562</sub> Examined by Hydrogen Exchange
80 Citations1998Ernesto J. Fuentes, A. Joshua Wand
Observations place a significant restraint upon the type of folding pathway that is operative for this protein and suggest that that the N- and C-terminal helices fold and unfold independently of the core of the molecule.
BiochemistryHydrogen exchange in unligated and ligated staphylococcal nuclease
77 Citations1993Stewart N. Loh, Kenneth E. Prehoda +2 more
Protection factors for the slowly exchanging hydrogens in unligated nuclease H124L at 37 degrees C and pH 5.5 were found to vary by over one order of magnitude, and exchange of these hydrogens thus appears to occur via global unfolding of the protein.
Nature Structural BiologyA model of the changes in denatured state structure underlying m value effects in staphylococcal nuclease.
64 Citations1999David Shortle, James O. Wrabl
Differences in exchange protection between the C-terminus and the β-barrel region correlate with mGuHCl, suggesting that a residual barrel-like structure becomes more highly populated in the denatured states of m- mutants and less populated in m+ mutants.
Folding and DesignCharacterization of the free energy spectrum of peptostreptococcal protein L
63 Citations1997Yi Qian, Michelle L. Scalley +3 more
For protein L under native conditions, there do not appear to be partially folded states with free energies intermediate between that of the folded and unfolded states.
StructureTouring the landscapes: partially folded proteins examined by hydrogen exchange
52 Citations1997Aaron K. Chamberlain, Susan Marqusee
Recent studies on Escherichia coli ribonuclease H and several other proteins reveal a specific region in each protein that remains structured in partially folded conformations that play a dominant role in determining the fold and stability.
Journal of Molecular BiologyLocal Perturbations by Ligand Binding of Hydrogen Deuterium Exchange Kinetics in a Four-helix Bundle Protein, Acyl Coenzyme A Binding Protein (ACBP)
49 Citations1995Birthe B. Kragelund, Jens Knudsen +1 more
The results suggest that hydrogen exchange kinetics in the individual sites of acyl-coenzyme A binding protein are primarily determined by local structural features, and show that ligand binding gives rise mainly to changes localized at the sites of interaction between protein and ligand.
Journal of Molecular BiologyHydrogen exchange kinetics of proteins in denaturants: a generalized two-process model † †Dedicated to Dr Andrew Morton, who tragically passed away on July 17, 1998, for the living memory of many long discussions on hydrogen exchange kinetics and protein folding intermediates. 1 1Edited by P. E. Wright
36 Citations1999Hong Qian, Sunney I. Chan
A comprehensive kinetic model for the site-specific HX of proteins under varying solvent denaturing conditions based on the two-state protein folding model, which suggests that the various observed intermediates of a protein can be interpreted as dominant isomers of either the folded or the unfolded state under different solvent conditions.
Proteins Structure Function and BioinformaticsTwo structural subdomains of barstar detected by rapid mixing NMR measurement of amide hydrogen exchange
36 Citations1998Abani K. Bhuyan, Jayant B. Udgaonkar
On the basis of the free energies of production of exchange‐competent states, the measured amide sites of barstar appear to define two structural subdomains—a three‐helix unit and a two‐β‐strand unit in the core of the protein.
Proceedings of the National Academy of SciencesA general two-process model describes the hydrogen exchange behavior of RNase A in unfolding conditions.
33 Citations1996Stewart N. Loh, Carol A. Rohl +2 more
The model predicts properties that are very different from the observed properties of the EX2 exchange reactions of RNase A in conditions where guanidine-induced unfolding takes place, and results and simulations indicate that moderate or high denaturant concentrations readily give rise to EX1 exchange in native proteins.
Proceedings of the National Academy of SciencesNative-state hydrogen-exchange studies of a fragment complex can provide structural information about the isolated fragments
25 Citations1999G. Chakshusmathi, Girish S. Ratnaparkhi +2 more
The studies suggest that folded RNase A and the RNase S complex exhibit very similar dynamic behavior, and that cleavage of a protein chain at a single site need not be accompanied by a large increase in flexibility of the complex relative to that of the uncleaved protein.
BiochemistryHydrogen-Exchange Stabilities of RNase T1 and Variants with Buried and Solvent-Exposed Ala → Gly Mutations in the Helix
24 Citations1999Beatrice M.P. Huyghues‐Despointes, U. Langhorst +3 more
Al Ala --> Gly mutations in the helix of RNase T1 at both helical positions alter the native-state hydrogen-exchange stabilities of residues throughout the sequence, indicating that the most stable residues are exchanging from the globally unfolded ensemble.
Trends in Biochemical SciencesHow much is a stabilizing bond worth?
17 Citations1994Kim A. Sharp, S. Walter Englander
In general, a bonding interaction contributes a free energy increment to protein or nucleic acid stability that is larger, an enthalpy increment that is smaller, and entropy and heat capacity increments that are more positive than the corresponding bond parameter.
BiochemistryInvestigation of the Structural Stability of Cardiotoxin Analogue III from the Taiwan Cobra by Hydrogen−Deuterium Exchange Kinetics
14 Citations1999Thirunavukkarasu Sivaraman, Thallapuranam Krishnaswamy Suresh Kumar +1 more
Comparison of the quenched-flow H/D exchange data on CTX III with those obtained in the present study reveals that the most slowly exchanging portion constitutes the folding core of the protein.