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Shorter Peptides (shorter + peptide)
Selected AbstractsThe role of disulfide bonds and N-terminus in the structural properties of hepcidins: Insights from molecular dynamics simulationsBIOPOLYMERS, Issue 10 2010Massimiliano Aschi Abstract The main purpose of this work is to analyse, by means of molecular dynamics (MD) simulations both structural and mechanical-dynamical differences between Hepcidin-20 and Hepcidin-25 in both oxidized and reduced states in aqueous solution. Results indicate that the presence of disulfide bonds is essential, in both peptides, for maintaining their ,-hairpin motif. As a matter of fact, the lack of this intra-peptide covalent interactions produces an almost immediate deviation from the oxidized, plausibly active, structure in both the systems. Interestingly, reduced Hepcidin-25 turns out to be characterized by a highly fluctuating structure which is found to rapidly span a large number of configurations at equilibrium. On the other hand, loss of disulfide bonds in the shorter peptide, results in a more compact and relatively rigid double-turn structure. Comparison of mechanical,dynamical properties and sidechains,sidechains interactions in oxidized Hepcidin-20 and Hepcidin-25 strongly suggest also the key role of N-terminus in the aggregation tendency of Hepcidin-25. © 2010 Wiley Periodicals, Inc. Biopolymers 93: 917,926, 2010. [source] Kinetic evidences for facilitation of peptide channelling by the proteasome activator PA28FEBS JOURNAL, Issue 20 2000Ralf Stohwasser The activation kinetics of constitutive and IFN,-stimulated 20S proteasomes obtained with homomeric (recPA28,, recPA28,) and heteromeric (recPA28,,) forms of recombinant 11S regulator PA28 was analysed by means of kinetic modelling. The activation curves obtained with increasing concentrations of the individual PA28 subunits (RecP28,/RecP28,/RecP28,+ RecP28,) exhibit biphasic characteristics which can be attributed to a low-level activation by PA28 monomers and full proteasome activation by assembled activator complexes. The dissociation constants do not reveal significant differences between the constitutive and the immunoproteasome. Intriguingly, the affinity of the proteasome towards the recPA28,, complex is about two orders of magnitude higher than towards the homomeric PA28, and PA28, complexes. Striking similarities can been revealed in the way how PA28 mediates the kinetics of latent proteasomes with respect to three different fluorogenic peptides probing the chymotrypsin-like, trypsin-like and peptidylglutamyl-peptide hydrolyzing like activity: (a) positive cooperativity disappears as indicated by a lack of sigmoid initial parts of the kinetic curves, (b) substrate affinity is increased, whereby (c), the maximal activity remains virtually constant. As these kinetic features are independent of the peptide substrates, we conclude that PA28 exerts its activating influence on the proteasome by enhancing the uptake (and release) of shorter peptides. [source] G,s protein C -terminal ,-helix at the interface: does the plasma membrane play a critical role in the G,s protein functionality?JOURNAL OF PEPTIDE SCIENCE, Issue 10 2005Stefania Albrizio Abstract The heterotrimeric guanine nucleotide-binding regulatory proteins (G proteins, G,,,) mediate the signalling process of a large number of receptors, known as G protein-coupled receptors. The C -terminal domain of the heterotrimeric G protein ,-subunit plays a key role in the selective activation of G proteins by their cognate receptors. The interaction of this domain can take place at the end of a cascade including several successive conformational modifications. G,s(350,394) is the 45-mer peptide corresponding to the C -terminal region of the G,s subunit. In the crystal structure of the G,s subunit it encompasses the ,4/,6 loop, the ,6 ,-sheet segment and the ,5 helix region. Following a previous study based on the synthesis, biological activity and conformational analysis of shorter peptides belonging to the same G,s region, G,s(350,394) was synthesized and investigated. The present study outlines the central role played by the residues involved in the ,4/,6 loop and ,6/,5 loops in the stabilization of the C -terminal G,s,-helix. H2O/2H2O exchange experiments, and NMR diffusion experiments show interesting evidence concerning the interaction between the SDS micelles and the polypeptide. These data prompt intriguing speculations on the role of the intracellular environment/cellular membrane interface in the stabilization and functionality of the C -terminal G,s region. Copyright © 2005 European Peptide Society and John Wiley & Sons, Ltd. [source] Structure of the Taz2 domain of p300: insights into ligand bindingACTA CRYSTALLOGRAPHICA SECTION D, Issue 12 2009Maria Miller CBP and its paralog p300 are histone acetyl transferases that regulate gene expression by interacting with multiple transcription factors via specialized domains. The structure of a segment of human p300 protein (residues 1723,1836) corresponding to the extended zinc-binding Taz2 domain has been investigated. The crystal structure was solved by the SAD approach utilizing the anomalous diffraction signal of the bound Zn ions. The structure comprises an atypical helical bundle stabilized by three Zn ions and closely resembles the solution structures determined previously for shorter peptides. Residues 1813,1834 from the current construct form a helical extension of the C-terminal helix and make extensive crystal-contact interactions with the peptide-binding site of Taz2, providing additional insights into the mechanism of the recognition of diverse transactivation domains (TADs) by Taz2. On the basis of these results and molecular modeling, a hypothetical model of the binding of phosphorylated p53 TAD1 to Taz2 has been proposed. [source] | ||||||||||