Browse
Submit Data
Databases
API
Help

Dataset Information

27 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Use of disulfide "staples" to stabilize beta-sheet quaternary structure.

ABSTRACT: This Letter reports the use of disulfide linkages to stabilize a beta-sheet dimer with a well-defined structure in aqueous and dimethyl sulfoxide solutions. In this dimer, two cyclic beta-sheet peptides are connected by disulfide linkages at the non-hydrogen-bonded rings. The cyclic beta-sheet "domains" interact through hydrogen bonding to form a four-stranded beta-sheet structure. This interaction results in enhanced folding of the cyclic beta-sheet peptides.

SUBMITTER: Khakshoor O

PROVIDER: S-EPMC2726807 | biostudies-literature | 2009 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Use of disulfide "staples" to stabilize beta-sheet quaternary structure.

Khakshoor Omid O Nowick James S JS

Organic letters 20090701 14

This Letter reports the use of disulfide linkages to stabilize a beta-sheet dimer with a well-defined structure in aqueous and dimethyl sulfoxide solutions. In this dimer, two cyclic beta-sheet peptides are connected by disulfide linkages at the non-hydrogen-bonded rings. The cyclic beta-sheet "domains" interact through hydrogen bonding to form a four-stranded beta-sheet structure. This interaction results in enhanced folding of the cyclic beta-sheet peptides. ...[more]

PMID: 19534505

Similar Datasets

Macrocyclic beta-sheet peptides that mimic protein quaternary structure through intermolecular beta-sheet interactions.

Project description:This paper reports the design, synthesis, and characterization of a family of cyclic peptides that mimic protein quaternary structure through beta-sheet interactions. These peptides are 54-membered-ring macrocycles comprising an extended heptapeptide beta-strand, two Hao beta-strand mimics [JACS 2000, 122, 7654] joined by one additional alpha-amino acid, and two delta-linked ornithine beta-turn mimics [JACS 2003, 125, 876]. Peptide 3a, as the representative of these cyclic peptides, contains a heptapeptide sequence (TSFTYTS) adapted from the dimerization interface of protein NuG2 [PDB ID: 1mio]. 1H NMR studies of aqueous solutions of peptide 3a show a partially folded monomer in slow exchange with a strongly folded oligomer. NOE studies clearly show that the peptide self-associates through edge-to-edge beta-sheet dimerization. Pulsed-field gradient (PFG) NMR diffusion coefficient measurements and analytical ultracentrifugation (AUC) studies establish that the oligomer is a tetramer. Collectively, these experiments suggest a model in which cyclic peptide 3a oligomerizes to form a dimer of beta-sheet dimers. In this tetrameric beta-sheet sandwich, the macrocyclic peptide 3a is folded to form a beta-sheet, the beta-sheet is dimerized through edge-to-edge interactions, and this dimer is further dimerized through hydrophobic face-to-face interactions involving the Phe and Tyr groups. Further studies of peptides 3b-3n, which are homologues of peptide 3a with 1-6 variations in the heptapeptide sequence, elucidate the importance of the heptapeptide sequence in the folding and oligomerization of this family of cyclic peptides. Studies of peptides 3b-3g show that aromatic residues across from Hao improve folding of the peptide, while studies of peptides 3h-3n indicate that hydrophobic residues at positions R3 and R5 of the heptapeptide sequence are important in oligomerization.

| S-EPMC2596933 | biostudies-literature

Analysis of the factors that stabilize a designed two-stranded antiparallel beta-sheet.

Project description:Autonomously folding beta-hairpins (two-strand antiparallel beta-sheets) have become increasingly valuable tools for probing the forces that control peptide and protein conformational preferences. We examine the effects of variations in sequence and solvent on the stability of a previously designed 12-residue peptide (1). This peptide adopts a beta-hairpin conformation containing a two-residue loop (D-Pro-Gly) and a four-residue interstrand sidechain cluster that is observed in the natural protein GB1. We show that the conformational propensity of the loop segment plays an important role in beta-hairpin stability by comparing 1 with (D)P--> N mutant 2. In addition, we show that the sidechain cluster contributes both to conformational stability and to folding cooperativity by comparing 1 with mutant 3, in which two of the four cluster residues have been changed to serine. Thermodynamic analysis suggests that the high loop-forming propensity of the (D)PG segment decreases the entropic cost of beta-hairpin formation relative to the more flexible NG segment, but that the conformational rigidity of (D)PG may prevent optimal contacts between the sidechains of the GB1-derived cluster. The enthalpic favorability of folding in these designed beta-hairpins suggests that they are excellent scaffolds for studying the fundamental mechanisms by which amino acid sidechains interact with one another in folded proteins.

| S-EPMC2373626 | biostudies-literature

Intramembranal disulfide cross-linking elucidates the super-quaternary structure of mammalian CatSpers.

Project description:CatSper is a voltage-dependent calcium channel located in the plasma membrane of the sperm flagellum and is responsible for triggering hyperactive motility. A homology model for the transmembrane region was built in which the arrangement of the subunits around the pseudo-four-fold symmetry axis was deduced by the pairing of conserved transmembranal cysteines across mammals. Directly emergent of the predicted quaternary structure is an architecture in which tetramers polymerize through additional, highly conserved cysteines, creating one or more double-rows channels extending the length of the principal piece of the mammalian sperm tail. The few species that are missing these cysteines are eusocial or otherwise monogamous, suggesting that sperm competition is selective for a disulfide-crosslinked macromolecular architecture. The model suggests testable hypotheses for how CatSper channel opening might behave in response to pH, 2-arachidonoylglycerol, and mechanical force. A flippase function is hypothesized, and a source of the concomitant disulfide isomerase activity is found in CatSper-associated proteins ?, ? and ?.

| S-EPMC6268196 | biostudies-literature

Misfolded opsin mutants display elevated β-sheet structure.

Project description:Mutations in rhodopsin can cause misfolding and aggregation of the receptor, which leads to retinitis pigmentosa, a progressive retinal degenerative disease. The structure adopted by misfolded opsin mutants and the associated cell toxicity is poorly understood. Förster resonance energy transfer (FRET) and Fourier transform infrared (FTIR) microspectroscopy were utilized to probe within cells the structures formed by G188R and P23H opsins, which are misfolding mutants that cause autosomal dominant retinitis pigmentosa. Both mutants formed aggregates in the endoplasmic reticulum and exhibited altered secondary structure with elevated β-sheet and reduced α-helical content. The newly formed β-sheet structure may facilitate the aggregation of misfolded opsin mutants. The effects observed for the mutants were unrelated to retention of opsin molecules in the endoplasmic reticulum itself.

| S-EPMC4641566 | biostudies-literature

Parallel ?-sheet secondary structure is stabilized and terminated by interstrand disulfide cross-linking.

Project description:Disulfide bonds between Cys residues in adjacent strands of parallel ?-sheets are rare among proteins, which suggests that parallel ?-sheet structure is not stabilized by such disulfide cross-links. We report experimental results that show, surprisingly, that an interstrand disulfide bond can stabilize parallel ?-sheets formed by an autonomously folding peptide in aqueous solution. NMR analysis reveals that parallel ?-sheet structure is terminated beyond the disulfide bond, which causes deviation from the extended backbone conformation at one of the Cys residues.

| S-EPMC3266109 | biostudies-literature

Toward beta-amino acid proteins: a cooperatively folded beta-peptide quaternary structure.

Project description:Folded polymers in nature are assembled from simple monomers and adopt complex folded structures through networks of stabilizing noncovalent interactions. These interactions define secondary and tertiary structure and in most cases specify a unique three-dimensional architecture. Individual secondary or tertiary structures can also associate with one another to form multi-subunit quaternary structures. Nonnatural folded polymers have potential for similar structural versatility. Here we describe a pair of beta3-peptides whose sequences were designed to promote a 14-helix structure in water, favor hetero-oligomer formation, and disfavor nonspecific aggregation. These beta3-peptides assemble noncovalently into a well-defined hetero-oligomer characterized by a defined stoichiometry, a highly stabilized secondary structure, and a cooperative melting transition (TM > 55 degrees C). This work demonstrates that beta3-peptides can assemble into defined, cooperatively folded quaternary structures and constitutes an important step toward designing protein-like assemblies from nonnatural polymers.

| S-EPMC2857659 | biostudies-literature

X-ray crystallographic structure of an artificial beta-sheet dimer.

Project description:This paper describes the X-ray crystallographic structure of a designed cyclic beta-sheet peptide that forms a well-defined hydrogen-bonded dimer that mimics beta-sheet dimers formed by proteins. The 54-membered ring macrocyclic peptide (1a) contains molecular template and turn units that induce beta-sheet structure in a heptapeptide strand that forms the dimerization interface. The X-ray crystallographic structure reveals the structures of the two "Hao" amino acids that help template the beta-sheet structure and the two delta-linked ornithine turn units that link the Hao-containing template to the heptapeptide beta-strand. The Hao amino acids adopt a conformation that resembles a tripeptide in a beta-strand conformation, with one edge of the Hao unit presenting an alternating array of hydrogen-bond donor and acceptor groups in the same pattern as that of a tripeptide beta-strand. The delta-linked ornithines adopt a conformation that resembles a hydrogen-bonded beta-turn, in which the ornithine takes the place of the i+1 and i+2 residues. The dimers formed by macrocyclic beta-sheet 1a resemble the dimers of many proteins, such as defensin HNP-3, the lambda-Cro repressor, interleukin 8, and the ribonuclease H domain of HIV-1 reverse transcriptase. The dimers of 1a self-assemble in the solid state into a barrel-shaped trimer of dimers in which the three dimers are arranged in a triangular fashion. Molecular modeling in which one of the three dimers is removed and the remaining two dimers are aligned face-to-face provides a model of the dimers of dimers of closely related macrocyclic beta-sheet peptides that were observed in solution.

| S-EPMC2929266 | biostudies-literature

Inter-molecular β-sheet structure facilitates lung-targeting siRNA delivery.

Project description:Size-dependent passive targeting based on the characteristics of tissues is a basic mechanism of drug delivery. While the nanometer-sized particles are efficiently captured by the liver and spleen, the micron-sized particles are most likely entrapped within the lung owing to its unique capillary structure and physiological features. To exploit this property in lung-targeting siRNA delivery, we designed and studied a multi-domain peptide named K-β, which was able to form inter-molecular β-sheet structures. Results showed that K-β peptides and siRNAs formed stable complex particles of 60 nm when mixed together. A critical property of such particles was that, after being intravenously injected into mice, they further associated into loose and micron-sized aggregates, and thus effectively entrapped within the capillaries of the lung, leading to a passive accumulation and gene-silencing. The large size aggregates can dissociate or break down by the shear stress generated by blood flow, alleviating the pulmonary embolism. Besides the lung, siRNA enrichment and targeted gene silencing were also observed in the liver. This drug delivery strategy, together with the low toxicity, biodegradability, and programmability of peptide carriers, show great potentials in vivo applications.

| S-EPMC4783658 | biostudies-literature

An artificial beta-sheet that dimerizes through parallel beta-sheet interactions.

Project description:This Article introduces a simple chemical model of a beta-sheet (artificial beta-sheet) that dimerizes by parallel beta-sheet formation in chloroform solution. The artificial beta-sheet consists of two N-terminally linked peptide strands that are linked with succinic or fumaric acid and blocked along one edge with a hydrogen-bonding template composed of 5-aminoanisic acid hydrazide. The template is connected to one of the peptide strands by a turn unit composed of (S)-2-aminoadipic acid (Aaa). 1H NMR spectroscopic studies show that these artificial beta-sheets fold in CDCl3 solution to form well-defined beta-sheet structures that dimerize through parallel beta-sheet interactions. Most notably, all of these compounds show a rich network of NOEs associated with folding and dimerization. The compounds also exhibit chemical shifts and coupling constants consistent with the formation of folded dimeric beta-sheet structures. The aminoadipic acid unit shows patterns of NOEs and coupling constants consistent with a well-defined turn conformation. The present system represents a significant step toward modeling the type of parallel beta-sheet interactions that occur in protein aggregation.

| S-EPMC2593858 | biostudies-literature

A new artificial beta-sheet that dimerizes through parallel beta-sheet interactions.

Project description:This paper introduces a chemical model of a beta-sheet that dimerizes through parallel beta-sheet interactions in CDCl(3) solution. The model consists of two C-terminally linked dipeptides connected to a molecular template. (1)H NMR studies establish the beta-sheet folding and dimerization of the model system. This system corroborates that linking two peptide strands and blocking one edge of the assembly creates soluble, easy-to-study systems that participate in the types of interactions that occur widely in peptide and protein aggregates.

| S-EPMC2652689 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data