A peptide model of a protein folding intermediate
NaturePublished 1 November 1988
Terrence G. Oas, Peter S. Kim
Citations251
SJR quartileQ1
SJR score18.29
SNIP10.16
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.
TL;DR
A disulphide-bonded peptide pair, designed to mimic the first crucial intermediate in the folding of bovine pancreatic trypsin inhibitor, contains secondary and tertiary structure similar to that found in the native protein.
Abstract
It is difficult to determine the structures of protein folding intermediates because folding is a highly cooperative process. A disulphide-bonded peptide pair, designed to mimic the first crucial intermediate in the folding of bovine pancreatic trypsin inhibitor, contains secondary and tertiary structure similar to that found in the native protein. Peptide models like this circumvent the problem of cooperativity and permit characterization of structures of folding intermediates.
Keywords
Biochemistry, Genetics and Molecular Biology
Journal of Molecular BiologyThe interpretation of protein structures: Estimation of static accessibility
5,888 Citations1971B. Lee, F.M. Richards
The accessibility of atoms in the twenty common amino acids in model tripeptides of the type Ala-X-Ala are given for defined conformation and the larger non-polar amino acids tend to be more “buried” in the native form of all three proteins.
BiochemistrySpectroscopic Determination of Tryptophan and Tyrosine in Proteins<sup>*</sup>
3,432 Citations1967Harold Edelhoch
A procedure is presented which strongly reduces or elimi- nates these interactions, normalizes their absorption, and consequently permits a more precise analysis of tryptophan and tyrosine in proteins.
Proceedings of the National Academy of SciencesTHE KINETICS OF FORMATION OF NATIVE RIBONUCLEASE DURING OXIDATION OF THE REDUCED POLYPEPTIDE CHAIN
1,199 Citations1961Christian B. Anfinsen, E Haber +2 more
There existed a considerable lag phase before enzymatic activity appeared after the sample of bovine pancreatic ribonuclease was treated with mercaptoethanol in urea, during which period the sulfhydrl titer and the specific optical rotation changed along a curve similar to that of a first-order reaction.
Annual Review of BiochemistrySpecific Intermediates in the Folding Reactions of Small Proteins and the Mechanism of Protein Folding
1,033 Citations1982Peter Kim, Robert L. Baldwin
NatureStructural characterization of folding intermediates in cytochrome c by H-exchange labelling and proton NMR
824 Citations1988Heinrich Röder, Gülnur A. Elöve +1 more
Results for cytochrome c show that the hydrogen exchange and rapid mixing method provides the spatial and temporal resolution necessary to monitor structure formation at many defined sites along the polypeptide chain on a timescale ranging from milliseconds to minutes.
Biopolymers<sup>1</sup>H‐nmr parameters of the common amino acid residues measured in aqueous solutions of the linear tetrapeptides H‐Gly‐Gly‐<i>X</i>‐<scp>L</scp>‐Ala‐OH
757 Citations1979Arno Bundi, Kurt Wüthrich
NatureProtein-folding dynamics
628 Citations1976Martin Karplus, D. L. Weaver
In a discussion of the dynamics of protein folding two limiting models (random-search nucleation and chain propagation., diffusion–collision) are considered and it is suggested that the latter may have the dominant role in many proteins.
NatureTests of the helix dipole model for stabilization of α-helices
603 Citations1987Kevin Shoemaker, Peter S. Kim +3 more
It is reported here that studies of C-peptide analogues support the helix dipole model, and provide further evidence for the importance of electrostatic interactions not included in the Zimm–Bragg model for α-helix formation.
NatureNMR evidence for an early framework intermediate on the folding pathway of ribonuclease A
580 Citations1988Jayant B. Udgaonkar, Robert L. Baldwin
A structural analysis of the intermediate by two-dimensional 1H-NMR is consistent with the framework model of protein folding in which stable secondary structure first forms the framework necessary for the subsequent formation of the complete tertiary structure.
Journal of Molecular BiologySequential resonance assignments in protein 1H nuclear magnetic resonance spectra
564 Citations1982Gerhard Wagner, Kurt Wüthrich
The assignment of the 1Hnuclear magnetic resonance spectrum of the basic pancreatic trypsin inhibitor with the use of two-dimensional 1H nuclear magnetic resonance techniques at 500 MHz is described.
Acta Crystallographica Section BCrystallographic refinement of the structure of bovine pancreatic trypsin inhibitor at l.5 Å resolution
549 Citations1975J. Deisenhofer, W. Steigemann
Journal of Protein ChemistryProtein folding: Hypotheses and experiments
545 Citations1987Oleg B. Ptitsyn
Experimental evidence on the existence of the novel “molten globule” state of the protein molecule and its role in protein folding are compared with the sequential model of protein folding proposed by the author in 1972–1973.
ScienceIntrinsic and Extrinsic Factors in Protein Antigenic Structure
481 Citations1985Jay A. Berzofsky
Which of these antibodies are made in any individual depends on factors extrinsic to the antigen molecule, host factors such as self-tolerance, immune response genes, idiotype networks, and the immunoglobulin structural gene repertoire.
Journal of Molecular BiologyStructure of bovine pancreatic trypsin inhibitor
473 Citations1984Alexander Wlodawer, J. Walter +2 more
The structure of form II crystals of bovine pancreatic trypsin inhibitor has been investigated by joint refinement of X-ray and neutron data and eleven amide hydrogens were found to be protected from exchange after three months of soaking the crystals in deuterated mother liquor at pH 8.2.
NatureTapping the immunological repertoire to produce antibodies of predetermined specificity
462 Citations1982Richard A. Lerner
This work has shown that chemically synthesized peptides representative of virtually any part of the surface of a protein can elicit antibodies reactive with the native molecule, and antibodies, useful in the study of changes in protein structure, can be generated.
BiochemistryFormation of three-dimensional structure in proteins. I. Rapid nonenzymic reactivation of reduced lysozyme
394 Citations1970Donald B. Wetlaufer, Vishesh Saxena
Journal of Molecular BiologyPacking of α-helices: Geometrical constraints and contact areas
364 Citations1978Timothy J. Richmond, Frederic M. Richards
Journal of Molecular BiologyKinetic role of a meta-stable native-like two-disulphide species in the folding transition of bovine pancreatic trypsin inhibitor
308 Citations1984Thomas E. Creighton, David P. Goldenberg
The unique information available about the formation and stabilities of the disulphides during refolding of reduced bovine pancreatic trypsin inhibitor provides a useful description of the way in which numerous weak interactions within a protein co-operate to produce a stable folded conformation.
Journal of Molecular BiologyHierarchic organization of domains in globular proteins
227 Citations1979George D. Rose
An automatic procedure is developed for the identification of domains in globular proteins from X-ray elucidated co-ordinates, and domains are shown to be iteratively decomposable into subdomains, leading to a hierarchic molecular architecture.
NatureThe immunodominant site of a synthetic immunogen has a conformational preference in water for a type-II reverse turn
226 Citations1985H. Jane Dyson, Keith J. Cross +4 more
Biophysical ChemistryA model of myoglobin self-organization
205 Citations1975Oleg B. Ptitsyn, Alexander A. Rashin
NatureA helix stop signal in the isolated S-peptide of ribonuclease A
188 Citations1984Peter S. Kim, Robert L. Baldwin
It is shown that the helix is limited to certain residues, including ones that are helical in the intact protein, and that a functional helix termination signal exists in the isolated peptide.
Journal of Molecular BiologyConformational restrictions on the pathway of folding and unfolding of the pancreatic trypsin inhibitor
185 Citations1977Thomas E. Creighton
It appears that essentially all elements of the native conformation are attained simultaneously in the final stage of folding, within an unstable and flexible, yet relatively compact, form of the entire polypeptide chain produced by weak interactions between groups distant in the primary structure.
Proceedings of the National Academy of SciencesHydrophobic basis of packing in globular proteins.
174 Citations1980George D. Rose, Shantanu Roy
The evidence suggests that linear chain regions rich in hydrophobic residues serve as small clusters that fold against each other, with concomitant or even later fixation of secondary structure.
Journal of Molecular BiologyA folding model of α-lactalbumin deduced from the three-state denaturation mechanism
174 Citations1977Kunihiro Kuwajima
Journal of Magnetic Resonance (1969)pH dependence of internal references
145 Citations1977Antonio De Marco
The Journal of Physical ChemistryThe problem of how and why proteins adopt folded conformations
115 Citations1985Thomas E. Creighton
Journal of Molecular BiologyThe single-disulphide intermediates in the refolding of reduced pancreatic trypsin inhibitor
107 Citations1974Thomas E. Creighton
The nature of the disulphide bonds present are concluded to reflect primarily the conformational forces acting at this stage of folding, which may be primarily interactions between segments with propensities for secondary structure, either helices or β-sheet.
BiochemistryCompact units in proteins
105 Citations1986Michael Zehfus, George D. Rose
An explicit measure of geometric compactness called the coefficient of compactness is introduced and is applied to lysozyme and ribonuclease to discover their constituent compact units.
Journal of Molecular BiologyConformations of intermediates in the folding of the pancreatic trypsin inhibitor
97 Citations1987David J. States, Thomas E. Creighton +2 more
Intermediates in the folding pathway of the bovine pancreatic trypsin inhibitor have been examined by 1H nuclear magnetic resonance and conformational features of the native protein are present in the intermediate containing just one of the three normal disulphide linkages.
Methods in enzymology on CD-ROM/Methods in enzymologySchematic drawings of protein structures
94 Citations1985Jane S. Richardson
A schematic drawing summarizes the overall features of a structure in a quickly graspable and relatively memorable form to communicate accurate three-dimensional information by utilizing all available monocular depth cues and, where possible, by mimicking the appearance of a binocular image.
BiochemistryKinetic analysis of the folding and unfolding of a mutant form of bovine pancreatic trypsin inhibitor lacking the cysteine-14 and -38 thiols
82 Citations1988David P. Goldenberg
The kinetics of the disulfide-coupled unfolding-refolding transition of a mutant form of bovine pancreatic trypsin inhibitor (BPTI) lacking Cys-14 and -38 were measured and compared to previous results for the wild-type protein and other modified forms, confirming the previous conclusion that the energetically preferred pathway for folding and unfolding of BPTI includes intramolecular rearrangements of intermediates.
BiopolymersEnergetics of protein structure and folding
78 Citations1985David P. Goldenberg, Thomas E. Creighton
The available experimental date on the kinetics of unfolding and refolding of small proteins are reviewed and a simple model is used to illustrate some of the aspects of protein‐folding energetics.
Journal of Molecular BiologyEffects of urea and guanidine · HCl on the folding and unfolding of pancreatic trypsin inhibitor
78 Citations1977Thomas E. Creighton
Concentrated solutions of urea and of guanidine · HCl produced a random spectrum of single-disulphide forms of the polypeptide chain of the pancreatic trypsin inhibitor, which confirms that these species are normally rapidly interconverted and that normal refolding of the reduced protein is not dependent kinetically upon residual stable conformation in the reducedprotein.
Journal of Molecular BiologyEvolutionary conservation and variation of protein folding pathways
69 Citations1983Michelle Hollecker, Thomas E. Creighton
Journal of Molecular BiologyA new two-disulphide intermediate in the refolding of reduced bovine pancreatic trypsin inhibitor
69 Citations1984David J. States, Christopher M. Dobson +2 more
The apparently complete refolding of reduced bovine pancreatic trypsin inhibitor is shown to produce a mixture of two species, one of which lacks the disulphide bond between cysteines 30 and 51, and its conformation for the understanding of protein folding is discussed.
Cold Spring Harbor Symposia on Quantitative BiologyProtein Architecture and the Origin of Introns
68 Citations1987Mitiko Go, Mizuho Nosaka
ScienceMutants of Bovine Pancreatic Trypsin Inhibitor Lacking Cysteines 14 and 38 Can Fold Properly
66 Citations1987Cara Marks, Hossein Naderi‐Manesh +3 more
Results indicate that, at physiological temperatures, BPTI lacking cysteines 14 and 38 can refold quantitatively, albeit at a rate somewhat slower than that exhibited by wild-type BPTi.
Journal of Molecular BiologyImmunochemical analysis of the conformational properties of intermediates trapped in the folding and unfolding of bovine pancreatic trypsin inhibitor
59 Citations1978Thomas E. Creighton, Edna Kalef +1 more
It is concluded that no segment of the polypeptide chain adopts a stable native-like conformation until the entire polypePTide chain is able to do so simultaneously.
Journal of Molecular BiologyBeta poly(l-lysine): A model system for biological self-assembly
55 Citations1974Raymond Hartman, Robert C. Schwaner +1 more
The finite size of the particles in this beta structure of poly( l -lysine) makes this system, in which assembly and conformation change are nearly inextricably linked, a possible model of self-assembling biological structures.
Journal of Molecular BiologyThe role of proline residues in the folding kinetics of the bovine pancreatic trypsin inhibitor derivative RCAM(14–38)
48 Citations1981Magali Jullien, Robert L. Baldwin
Criteria based on folding kinetics are given for classifying the types of folding reaction shown by unfolded molecules containing a single wrong proline isomer, and it is pointed out that the type of folding Reaction depends also on the folding conditions, and a possible explanation for this effect is given.
Antibodies Against Synthetic Peptides
48 Citations1983Gernot Walter, Russell F. Doolittle
Advances in the field of DNA sequencing have provided a plethora of sequence information about proteins, real and putative, many of which have never been isolated, never mind characterized.
Journal of Molecular BiologyRole of the environment in the refolding of reduced pancreatic trypsin inhibitor
46 Citations1980Thomas E. Creighton
Refolding of reduced pancreatic trypsin inhibitor has been examined under a variety of environmental conditions, varying the temperature, pH and ions of the solution, and determining the transient intermediates that accumulate and the kinetics of refolding.
BiochemistryCircular dichroism spectroscopy of the intermediates that precede the rate-limiting step of the refolding pathway of bovine pancreatic trypsin inhibitor. Relationship of conformation and the refolding pathway
42 Citations1983Phyllis Anne Kosen, Thomas E. Creighton +1 more
All the spectra show that nonrandom conformations of the polypeptide chain gradually appear as disulfide bond formation progresses, as expected from the nonrandom pathway of the latter.
Journal of Molecular BiologyReactivities of the cysteine residues of the reduced pancreatic trypsin inhibitor
36 Citations1975Thomas E. Creighton
The results corroborate the previous conclusion that all six cysteine residues participate in forming the first disulphide bond during refolding of the reduced inhibitor and confirm that disulPHide bond formation is an accurate probe of the conformational transitions that occur during protein folding.
Biophysical ChemistryKinetics of the disordered chain-to-β transformation of Poly(L-Tyrosine) in aqueous solution
21 Citations1976Henry Auer, Elizabeth Patton
The kinetics of the transformation of poly(L-tyrosine) from the disordered chain to the intramolecular beta structure in aqueous solution has been studied andSharp pH-dependent maxima in the phenomenological rate constants and in the fractional amplitude of the rapid step were found.
Journal of Molecular BiologyRefolding of bovine pancreatic trypsin inhibitor modified at methionine-52
19 Citations1978Thomas E. Creighton, Douglas F. Dyckes +1 more
The reduced fragment of pancreatic trypsin inhibitor lacking the six C-terminal residues, which is produced by cyanogen bromide cleavage, formed a seemingly random mixture of disulphide bonds under refolding conditions where normal pancreatictrypsin inhibitors refolds correctly and quantitatively illustrates the importance of the C- terminal residues in folding of the normal protein.
BiochemistryConformational studies on the β subunits of human hemoglobin and their arginyl-COOH peptides
17 Citations1975Clara Fronticelli-Bucci, Enrico Bucci
The beta subunits of hemoglobin upon alkylation of the cysteinyl residues with iodoacetamide showed a sedimentation velocity with an S20w, near 1.8 as for monomeric subunits, and upon removal of the heme the apo-beta subunits showed a decreased optical activity in the far-uv region of the spectrum indicating a substantial loss of helical content.
BiopolymersFolding of protein fragments: Conformational and biological studies on thioredoxin and its fragments
11 Citations1983Herbert Reutimann, Pier Luigi Luisi +1 more
It is shown that the (1–37) fragment, which contains the active disulfide unit center, is present as an unordered structure in the neutral pH range, but assumes a rigid folding at pH values below 6.5.