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Hairpin Conformation (hairpin + conformation)
Selected AbstractsDesign of Neutral Metallomesogens from 5,5-Dimethyldipyrromethane: Metal Ion Mediated Control of Folding and Hairpin StructuresEUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 32 2008Kelly A. Ames Abstract New ligands derived from 5,5-dimethyldipyrromethane and their corresponding neutral complexes with ZnII and PdII are described. The ligands incorporate either a hexacatenar [H2(1n), n = 1, 10, 12, 14 and 16], tetracatenar [H2(2n), n = 1 and 16] or an extended dicatenar structure [H2(3n), n = 1and 16]. Single-crystal X-ray structure determinations of [Zn2(11)2] and [Zn2(31)2] confirm a distorted tetrahedral geometry at ZnII to afford double-stranded helical structures, while the PdII species [Pd(31)] shows a distorted square-planar geometry with the ligand adopting an alternative hairpin conformation. The metal-free hexacatenar ligands H2(1n) (n = 10, 12, 14, 16) and the corresponding complexes [Zn2(116)2] and [Pd(1n)] (n = 12, 14, 16) are not mesomorphic. However, the tetracatenar complex [Zn2(216)2] generates a smectic mesophase, as confirmed by X-ray diffraction, while [Pd(216)] and the metal-free ligand H2(216) show no mesomorphic behaviour. Two of the extended dicatenar compounds, H2(316) and [Zn2(316)2] are non-mesomorphic, while [Pd(316)] displays a smectic A phase.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008) [source] Crystal structures of Nipah and Hendra virus fusion core proteinsFEBS JOURNAL, Issue 19 2006Zhiyong Lou The Nipah and Hendra viruses are highly pathogenic paramyxoviruses that recently emerged from flying foxes to cause serious disease outbreaks in humans and livestock in Australia, Malaysia, Singapore and Bangladesh. Their unique genetic constitution, high virulence and wide host range set them apart from other paramyxoviruses. These characteristics have led to their classification into the new genus Henpavirus within the family Paramyxoviridae and to their designation as Biosafety Level 4 pathogens. The fusion protein, an enveloped glycoprotein essential for viral entry, belongs to the family of class I fusion proteins and is characterized by the presence of two heptad repeat (HR) regions, HR1 and HR2. These two regions associate to form a fusion-active hairpin conformation that juxtaposes the viral and cellular membranes to facilitate membrane fusion and enable subsequent viral entry. The Hendra and Nipah virus fusion core proteins were crystallized and their structures determined to 2.2 Å resolution. The Nipah and Hendra fusion core structures are six-helix bundles with three HR2 helices packed against the hydrophobic grooves on the surface of a central coiled coil formed by three parallel HR1 helices in an oblique antiparallel manner. Because of the high level of conservation in core regions, it is proposed that the Nipah and Hendra virus fusion cores can provide a model for membrane fusion in all paramyxoviruses. The relatively deep grooves on the surface of the central coiled coil represent a good target site for drug discovery strategies aimed at inhibiting viral entry by blocking hairpin formation. [source] A model of a gp120 V3 peptide in complex with an HIV-neutralizing antibody based on NMR and mutant cycle-derived constraintsFEBS JOURNAL, Issue 3 2000Anat Zvi The 0.5, monoclonal antibody is a very potent strain-specific HIV-neutralizing antibody raised against gp120, the envelope glycoprotein of HIV-1. This antibody recognizes the V3 loop of gp120, which is a major neutralizing determinant of the virus. The antibody,peptide interactions, involving aromatic and negatively charged residues of the antibody 0.5,, were studied by NMR and double-mutant cycles. A deuterated V3 peptide and a Fab containing deuterated aromatic amino acids were used to assign these interactions to specific V3 residues and to the amino acid type and specific chain of the antibody by NOE difference spectroscopy. Electrostatic interactions between negatively charged residues of the antibody Fv and peptide residues were studied by mutagenesis of both antibody and peptide residues and double-mutant cycles. Several interactions could be assigned unambiguously: F96(L) of the antibody interacts with Pro13 of the peptide, H52(H) interacts with Ile7, Ile9 and Gln10 and D56(H) interacts with Arg11. The interactions of the light-chain tyrosines with Pro13 and Gly14 could be assigned to either Y30a(L) and Y32(L), respectively, or Y32(L) and Y49(L), respectively. Three heavy-chain tyrosines interact with Ile7, Ile20 and Phe17. Several combinations of assignments involving Y32(H), Y53(H), Y96(H) and Y100a(H) may satisfy the NMR and mutagenesis constraints, and therefore at this stage the interactions of the heavy-chain tyrosines were not taken into account. The unambiguous assignments [F96(L), H52(H) and D56(H)] and the two possible assignments of the light-chain tyrosines were used to dock the peptide into the antibody-combining site. The peptide converges to a unique position within the binding site, with the RGPG loop pointing into the center of the groove formed by the antibody complementary determining regions while retaining the ,-hairpin conformation and the type-VI RGPG turn [Tugarinov, V., Zvi, A., Levy, R. & Anglister, J. (1999) Nat. Struct. Biol.6, 331,335]. [source] Analysis of the factors that stabilize a designed two-stranded antiparallel ,-sheetPROTEIN SCIENCE, Issue 6 2002Juan F. Espinosa Abstract Autonomously folding ,-hairpins (two-strand antiparallel ,-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 ,-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 ,-hairpin stability by comparing 1 with DP, 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 DPG segment decreases the entropic cost of ,-hairpin formation relative to the more flexible NG segment, but that the conformational rigidity of DPG may prevent optimal contacts between the sidechains of the GB1-derived cluster. The enthalpic favorability of folding in these designed ,-hairpins suggests that they are excellent scaffolds for studying the fundamental mechanisms by which amino acid sidechains interact with one another in folded proteins. [source] Structural analysis of the complex of Keap1 with a prothymosin , peptideACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 4 2008Balasundaram Padmanabhan The Nrf2 transcription factor, which plays important roles in oxidative and xenobiotic stress, is negatively regulated by the cytoplasmic repressor Keap1. The ,-propeller/Kelch domain of Keap1, which is formed by the double-glycine repeat and C-terminal region domains (Keap1-DC), interacts directly with the Neh2 domain of Nrf2. The nuclear oncoprotein prothymosin , (ProT,) also interacts directly with Keap1 and may play a role in the dissociation of the Keap1,Nrf2 complex. The structure of Keap1-DC complexed with a ProT, peptide (amino acids 39,54) has been determined at 1.9,Å resolution. The Keap1-bound ProT, peptide possesses a hairpin conformation and binds to the Keap1 protein at the bottom region of the ,-propeller domain. Complex formation occurs as a consequence of their complementary electrostatic interactions. A comparison of the present structure with recently reported Keap1-DC complex structures revealed that the DLG and ETGE motifs of the Neh2 domain of Nrf2 and the ProT, peptide bind to Keap1 in a similar manner but with different binding potencies. [source] Gene conversion causing human inherited disease: Evidence for involvement of non-B-DNA-forming sequences and recombination-promoting motifs in DNA breakage and repair,HUMAN MUTATION, Issue 8 2009Nadia Chuzhanova Abstract A variety of DNA sequence motifs including inverted repeats, minisatellites, and the , recombination hotspot, have been reported in association with gene conversion in human genes causing inherited disease. However, no methodical statistically based analysis has been performed to formalize these observations. We have performed an in silico analysis of the DNA sequence tracts involved in 27 nonoverlapping gene conversion events in 19 different genes reported in the context of inherited disease. We found that gene conversion events tend to occur within (C+G)- and CpG-rich regions and that sequences with the potential to form non-B-DNA structures, and which may be involved in the generation of double-strand breaks that could, in turn, serve to promote gene conversion, occur disproportionately within maximal converted tracts and/or short flanking regions. Maximal converted tracts were also found to be enriched (P<0.01) in a truncated version of the ,-element (a TGGTGG motif), immunoglobulin heavy chain class switch repeats, translin target sites and several novel motifs including (or overlapping) the classical meiotic recombination hotspot, CCTCCCCT. Finally, gene conversions tend to occur in genomic regions that have the potential to fold into stable hairpin conformations. These findings support the concept that recombination-inducing motifs, in association with alternative DNA conformations, can promote recombination in the human genome. Hum Mutat 30:1,10, 2009. © 2009 Wiley-Liss, Inc. [source] The sequence TGAAKAVALVL from glyceraldehyde-3-phosphate dehydrogenase displays structural ambivalence and interconverts between ,-helical and ,-hairpin conformations mediated by collapsed conformational statesJOURNAL OF PEPTIDE SCIENCE, Issue 5 2007Sunita Patel Abstract The peptide TGAAKAVALVL from glyceraldehyde-3-phosphate dehydrogenase adopts a helical conformation in the crystal structure and is a site for two hydrated helical segments, which are thought to be helical folding intermediates. Overlapping sequences of four to five residues from the peptide, sample both helical and strand conformations in known protein structures, which are dissimilar to glyceraldehyde-3-phosphate dehydrogenase suggesting that the peptide may have a structural ambivalence. Molecular dynamics simulations of the peptide sequence performed for a total simulation time of 1.2 µs, starting from the various initial conformations using GROMOS96 force field under NVT conditions, show that the peptide samples a large number of conformational forms with transitions from ,-helix to ,-hairpin and vice versa. The peptide, therefore, displays a structural ambivalence. The mechanism from ,-helix to ,-hairpin transition and vice versa reveals that the compact bends and turns conformational forms mediate such conformational transitions. These compact structures including helices and hairpins have similar hydrophobic radius of gyration (Rgh) values suggesting that similar hydrophobic interactions govern these conformational forms. The distribution of conformational energies is Gaussian with helix sampling lowest energy followed by the hairpins and coil. The lowest potential energy of the full helix may enable the peptide to take up helical conformation in the crystal structure of the glyceraldehyde-3-phosphate dehydrogenase, even though the peptide has a preference for hairpin too. The relevance of folding and unfolding events observed in our simulations to hydrophobic collapse model of protein folding are discussed. Copyright © 2007 European Peptide Society and John Wiley & Sons, Ltd. [source] | ||||||||||