Helix In Solution Research Articles

Uncoiling transition for DNA in solution.

We study a simple DNA helix model, consisting of two infinite chains of evenly spaced charges to represent the phosphate groups, wound in a helix which lies on an imaginary cylindrical surface. The change in the free energy per helix charge between coiled and uncoiled conformations of the helix in solution is studied as a function of the charge per unit length along the helix axis. This allows us to study the effects of the solution on the helix stability and coiling. The change in the free energy is calculated from Soumpasis's pair potential of mean force, applied to all pairs of helix charges [D. M. Soumpasis, Proc. Natl. Acad. Sci. U.S.A. 81, 5116 (1984)]. The local counterion concentration is calculated from the counterion radial distribution that results from solving the Poisson-Boltzmann equation for an infinite uniformly charged cylinder [R. M. Fuoss, A. Katchalsky, and S. Lifson, Proc. Natl. Acad. Sci. 37, 579 (1951)], whose linear charge density is equal to the charge per unit length along the helix axis. Our results show that the helix is less stable on decreasing bulk dielectric constant and more stable on increasing counterion radius. Experimental data are discussed on DNA in solutions with water, ethanol, and methanol as the solvent. \textcopyright{} 1996 The American Physical Society.

Structural features and stability of an RNA triple helix in solution.

A 30 nt RNA with a sequence designed to form an intramolecular triple helix was analyzed by one-and two-dimensional NMR spectroscopy and UV absorption measurements. NMR data show that the RNA contains seven pyrimidine-purine-pyrimidine base triples stabilized by Watson-Crick and Hoogsteen interactions. The temperature dependence of the imino proton resonances, as well as UV absorption data, indicate that the triple helix is highly stable at acidic pH, melting in a single sharp transition centered at 62 degrees C at pH 4.3. The Watson-Crick and Hoogsteen pairings are disrupted simultaneously upon melting. The NMR data are consistent with a structural model where the Watson-Crick paired strands form an A-helix. Results of model building, guided by NMR data, suggest a possible hydrogen bond between the 2' hydroxyl proton of the Hoogsteen strand and a phosphate oxygen of the purine strand. The structural model is discussed in terms of its ability to account for some of the differences in stability reported for RNA and DNA triple helices and provides insight into features that are likely to be important in the design of RNA binding compounds.

Template synthesis of helicates of a [2 + 2] tetraimine macrocycle: crystal structure of the lead(II) perchlorate complex

The Schiff-base condensation of α,α′-bis(2-aminophenoxy)-o-xylene and pyridine-2,6-dicarbaldehyde produced mononuclear complexes of the same [2 + 2] cyclocondensation product L1 in the presence of divalent metal ions ranging in size from MnII to BaII. The origin of the apparent insensitivity of the synthesis to the metal-ion size lies in the ability of the resulting 34-membered macrocycle to adopt either of two distinct co-ordination modes featuring double helical configurations stabilised by intramolecular π–π interactions. The crystal structure of [PbL1][ClO4]2·4MeCN [trigonal, space group Pc1, a=b= 20.557(3), c= 23.843(3)A, R= 0.0499, R′= 0.0440] shows the metal ion co-ordinated by the N6O4 donor set of the macrocycle within a fulldouble helical ligand array stabilised by five separate aromatic π–π interactions. Proton NMR studies of the diamagnetic complexes of L1, assisted by detailed assignments of aromatic subspectra, provided evidence for retention of molecular helicity in solution; an interesting example of T1-spin decoupling of 207Pb is noted in the field-dependent spectra of [PbL1][ClO4]2 in CD3CN.

The α-helix as seen from the protein tertiary structure: a 3-D structural classification

Helices are selected from globular protein structures defined at high resolution by X-ray analysis. We cluster α-helices in two ways: according to their position in the tertiary structure by considering patterns of solvent inaccessible residues and according to the arc of the solvent inaccessible face. For each class of helices we have defined propensities for amino acids at each position; these can be used to calculate templates for recognition of a member of that class. The analysis provides a basis for the prediction of α-helices and estimation of their approximate position in a protein tertiary structure. It also provides an approach to estimating the probability of finding amino acid sequences as helices in solution and in a folded protein, thus indicating those helices that might be involved in nucleation of protein folding.

Self-assembly of the first heterodinuclear d–f triple helix in solution

The segmental bidentate–tridentate ligand L2 reacts with LnIII and ZnII in acetonitrile to give the first self-assembled heterodinuclear d–f triple-helical complexes [LnZn(L2)3]5+(Ln = La, Eu), as determined from solution-phase studies.

Contrasting solution conformations of peptides containing α,α‐dialkylated residues with linear and cyclic side chains

The conformational properties of alpha,alpha-dialkylated amino acid residues possessing acyclic (diethylglycine, Deg; di-n-propylglycine, Dpg; di-n-butylglycine, Dbg) and cyclic (1-aminocycloalkane-1-carboxylic acid, Acnc) side chains have been compared in solution. The five peptides studied by nmr and CD spectroscopy are Boc-Ala-Xxx-Ala-OMe, where Xxx = Deg (I), Dpg (II), Dbg (III), Ac6c (IV), and Ac7c (V). Delineation of solvent-shielded NH groups have been achieved by solvent and temperature dependence of NH chemical shifts in CDCl3 and (CD3)2SO and by paramagnetic radical induced line broadening in peptide III. In the Dxg peptides the order of solvent exposure of NH groups is Ala(1) > Ala(3) > Dxg(2), whereas in the Acnc peptides the order of solvent exposure of NH groups is Ala(1) > Acnc(2) > Ala(3). The nmr results suggest that Acnc peptides adopt folded beta-turn conformations with Ala(1) and Acnc(2) occupying i + 1 and i + 2 positions. In contrast, the Dxg peptides favor extended C5 conformations. The conformational differences in the two series are clearly borne out in CD studies. The solution conformations of peptides I-III are distinctly different from the beta-turn structure observed in crystals. Low temperature nmr spectra recorded immediately after dissolution of crystals of peptide II provide evidence for a structural transition. Introduction of an additional hydrogen-bonding function in Boc-Ala-Dpg-Ala-NHMe (VI) results in a stabilization of a consecutive beta-turn or incipient 3(10)-helix in solution.

Spectroscopic evidence for an intramolecular RNA triple helix

A 29-base RNA oligomer has been chemically synthesized and shown to form an intramolecular triple helix in solution at acidic pH. Assignment of the majority of the exchangeable proton NMR resonances demonstrated the Watson—Crick and Hoogsteen base pairings consistent with folding to form pyrimidine—purine—pyrimidine base triplets. FTIR spectroscopy provided independent evidence of base triplet formation, and indicated a predominately C3′-endo sugar pucker. UV absorption as a function of temperature suggested monophasic melting behaviour, which was confirmed by NMR of the imino protons.

The double pi pi 5.6 helix of gramicidin A predominates in unsaturated lipid membranes.

The structure of the channel-forming polypeptide gramicidin A (GA) incorporated into phosphatidyl-choline (PC) liposomes has been studied as a function of the degree of unsaturation of the acyl chains of PC. The initial conformational state of GA in reconstituted bilayers is determined by the solvent in which the peptide and the lipid are initially co-dissolved, whereas the equilibrium conformational state (after heat incubation) is affected by the lipid structure rather than by the nature of the solvent. The conformational equilibrium of GA has been studied in liposomes prepared from PC having a variable number of double bonds in the fatty acid moiety, by circular dichroism and Fourier transform infrared. Liposomes were prepared from trifluoroethanol or ethanol solutions and incubated at 68 degrees C. GA was shown to retain the conformation of the right-handed pi-->6.3 pi<--6.3 helix in PC with saturated acyl chains and with one double bond, whereas in dilinoleoyl-PC, having two double bond in each chain, the thermodynamically preferred structures are left-handed antiparallel and parallel double pi pi 5.6 helices. Natural soybean PC also favours left-handed pi pi 5.6 helical structures of GA (approximately 75%). This finding is discussed in terms of the role of PC unsaturation in the dynamic properties of the lipid matrix. Differences between observed FTIR spectra of the increases decreases pi pi 5.6 helix in solution (and to a larger extent in the membrane) and the calculated IR spectra can be interpreted as resulting from deviation of the real structure from the theoretically derived ideal helix. The data obtained provide grounds for better understanding of a GA channel functioning in lipids of variable degrees of unsaturation.

RNA recognition by an isolated α helix

A 17 amino acid peptide containing the arginine-rich region of the HIV Rev protein binds specifically to Rev response element (RRE) RNA. Even though it is highly charged, the peptide forms an α helix in solution, but only when its N- and C-termini are modified to provide favorable electrostatic interactions with the helix macrodipole. Binding affinity for IIB RNA (the primary binding site within the RRE) increases with α helix content, whereas nonspecific binding affinity is independent of helix content. Binding of mutant peptides demonstrates that one threonine, one asparagine, and four arginine side chains are important for sequence-specific recognition. Transactivation of the HIV LTR using Tat-Rev peptide hybrids and the RRE IIB site indicates that the peptide adopts an α-helical conformation in vivo. The results suggest that interactions with the RNA backbone may help to orient the α helix in the major groove of RNA.

Unfolding of an α‐helix in peptide crystals by solvation: Conformational fragility in a heptapeptide

The structure of the peptide Boc-Val-Ala-Leu-Aib-Val-Ala-Leu-OMe has been determined in crystals obtained from a dimethylsulfoxide-isopropanol mixture. Crystal parameters are as follows: C38H69N7O10.H2O.2C3H7OH, space group P2(1), a = 10.350 (2) A b = 26.084 (4) A, c = 10.395 (2) A, beta = 96.87 (12), Z = 2, R = 8.7% for 2686 reflections observed > 3.0 sigma (F). A single 5-->1 hydrogen bond is observed at the N-terminus, while two 4-->1 hydrogen bonds characteristic of a 3(10)-helix are seen in the central segment. The C-terminus residues, Ala(6) and Leu(7) are extended, while Val(5) is considerably distorted from a helical conformation. Two isopropanol molecules make hydrogen bonds to the C-terminal segment, while a water molecule interacts with the N-terminus. The structure is in contrast to that obtained for the same peptide in crystals from methanol-water [I. L. Karle, J. L. Flippen-Anderson, K. Uma, and P. Balaram (1990) Proteins: Structure, Function and Genetics, Vol. 7, pp. 62-73] in which two independent molecules reveal an almost perfect alpha-helix and a helix penetrated by a water molecule. A comparison of the three structures provides a snapshot of the progressive effects of solvation leading to helix unwinding. The fragility of the heptapeptide helix in solution is demonstrated by nmr studies in CDCl3 and (CD3)2SO. A helical conformation is supported in the apolar solvent CDCl3, whereas almost complete unfolding is observed in the strongly solvating medium (CD3)2SO.

Physical reasons for secondary structure stability: α‐Helices in short peptides

It was recently found that some short peptides (including C- and S-peptide fragments of RNase A) can have considerable helicity in solution, which was considered to be surprising. Does the observed helicity require a new explanation, or is it consistent with previous understanding? In this work we show that this helicity is consistent with the physical theory of secondary structure based on an extension of the conventional Zimm-Bragg model. Without any special modifications, this theory explains reasonably well almost all the experimentally observed dependencies of helicity on pH, temperature, and amino acid replacements. We conclude that the observed "general level" of helicity of C- and S-peptides (5-30% at room temperature and 10-50% near 0 degrees C) is "normal" for short peptides consisting mainly of helix-forming and helix-indifferent residues. The helicity is modified by a multitude of weak specific side chain interactions, many of which are taken into account by the present theory; some discrepancies between the theory and experiment can be explained by weak side-chain-side chain interactions that were neglected. A reasonable coincidence of the theory with experiment suggests that it had been used to investigate the role of local interactions in the formation of alpha-helical "embryos" in unfolded protein chains.

X-ray scattering indicates that the leucine zipper is a coiled coil.

Dimerization of the bZIP class of eukaryotic transcriptional control proteins requires a sequence motif called the leucine zipper. We have grown two distinct crystal forms of a 33-amino acid peptide corresponding to the leucine zipper of the yeast transcriptional activator GCN4. This peptide is known to form a dimer of parallel helices in solution. X-ray scattering from both crystal forms shows reflections that are diagnostic of coiled coils. The most notable reflections occur at approximately 5.2 A resolution and correspond to the pitch of helices in coiled coils. There is no diffraction maximum near 5.4 A, the characteristic pitch of straight helices. Our results provide direct evidence that the leucine zipper of GCN4 is a coiled coil.

Structure and stability of a DNA triple helix in solution: NMR studies on d(T)6.cntdot.d(A)6.cntdot.d(T)6 and its complex with a minor groove binding drug

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTStructure and stability of a DNA triple helix in solution: NMR studies on d(T)6.cntdot.d(A)6.cntdot.d(T)6 and its complex with a minor groove binding drugKimiko Umemoto, Mukti H. Sarma, Goutam Gupta, Jia Luo, and Ramaswamy H. SarmaCite this: J. Am. Chem. Soc. 1990, 112, 11, 4539–4545Publication Date (Print):May 1, 1990Publication History Published online1 May 2002Published inissue 1 May 1990https://doi.org/10.1021/ja00167a063RIGHTS & PERMISSIONSArticle Views142Altmetric-Citations49LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (819 KB) Get e-Alerts Get e-Alerts

RNA bulges and the helical periodicity of double-stranded RNA

RNA molecules typically exhibit extensive secondary structure, including double-stranded duplex, hairpins, internal loops, bulged bases and pseudoknotted structures (reviewed in refs 3 and 4). This is intimately connected with biological function, including splicing reactions and ribozyme activity. The formation of RNA-DNA hybrids is important in the transcription of DNA, reverse transcription of viral RNA, and DNA replication. Bulged bases in RNA helices are potentially significant in RNA folding and in providing sites for specific protein-RNA interactions, as illustrated by TFIIIA of Xenopus and the coat protein of phage R17. Most information about the structure of RNA derives from fibre diffraction or crystallography of natural molecules, notably transfer RNA, but until recently there have been few systematic studies of RNA structure using designed sequences. We have used gel electrophoresis to investigate the properties of bulged bases in both RNA and RNA-DNA depending on the number and types of bases in the bulge and its position in the fragment. By varying the spacing between two bulge-induced kinks, we have measured the periodicity of RNA and RNA-DNA helices in solution.

NMR studies of DNA (R+)n.(Y-)n.(Y+)n triple helices in solution: imino and amino proton markers of T.A.T and C.G.C+ base-triple formation.

High-resolution exchangeable proton two-dimensional NMR spectra have been recorded on 11-mer DNA triple helices containing one oligopurine (R)n and two oligopyrimidine (Y)n strands at acidic pH and elevated temperatures. Our two-dimensional nuclear Overhauser effect studies have focused on an 11-mer triplex where the third oligopyrimidine strand is parallel to the oligopurine strand. The observed distance connectivities establish that the third oligopyrimidine strand resides in the major groove with the triplex stabilized through formation of T.A.T and C.G.C+ base triples. The T.A.T base triple can be monitored by imino protons of the thymidines involved in Watson-Crick (13.65-14.25 ppm) and Hoogsteen (12.9-13.55 ppm) pairing, as well as the amino protons of adenosine (7.4-7.7 ppm). The amino protons of the protonated (8.5-10.0 ppm) and unprotonated (6.5-8.3 ppm) cytidines in the C.G.C+ base triple provide distinct markers as do the imino protons of the guanosine (12.6-13.3 ppm) and the protonated cytidine (14.5-16.0 ppm). The upfield chemical shift of the adenosine H8 protons (7.1-7.3 ppm) establishes that the oligopurine strand adopts an A-helical base stacking conformation in the 11-mer triplex. These results demonstrate that oligonucleotide triple helices can be readily monitored by NMR at the individual base-triple level with distinct markers differentiating between Watson-Crick and Hoogsteen pairing. Excellent exchangeable proton spectra have also been recorded for (R+)n.(Y-)n.(Y+)n 7-mer triple helices with the shorter length permitting spectra to be recorded at ambient temperature.(ABSTRACT TRUNCATED AT 250 WORDS)

Harmonic and subharmonic resonances of microwave absorption in DNA.

We have studied theoretically the movement of large molecular groups of DNA double helices in solution, which are driven by the electromagnetic field. The longitudinal vibration of nucleotides and the torsional movement of bases are taken into account at the same time. A set of coupled nonlinear partial differential equations has been established, and we have solved these equations by the method of perturbation. The result shows that there exists resonant absorption of microwave energy for both longitudinal and torsional modes. The resonant frequencies for the former and the latter are in the region of gigahertz and subterahertz, respectively. In addition to an nth-harmonic resonance at ${\ensuremath{\omega}}_{n}$, our theory also predicts a subharmonic resonance at ${\ensuremath{\omega}}_{n}$/2. The strength of the latter is proportional to ${l}^{\mathrm{\ensuremath{-}}3}$, where l is the length of DNA. The necessary conditions to observe these resonances are also discussed.

らせん構造を有する光学活性高分子の合成と利用

Helix is the most important, interesting structure for polymers. One-handed helical structure can be optically active without any other chiral factors. This review describes mainly the synthesis, structure, and utilization of helical polymers obtained from both chiral and achiral monomers. The monomers dealt with here include methacrylates, isocyanides, chloral, and isocyanates. Triarylmethyl methacrylates afford helical polymers by anionic polymerization. Some of the polymers slowly change their helicity in solution. Application of the polymers as chiral stationary phases to separate optical isomers is discussed. Bulky isocyanides and chloral give optically active polymers which have the chirality arising only from helicity. Polyisocyanates leads to a large optical activity due to a cooperative deuterium isotope effect. These are also surveyed with an emphasis on the helicity.

Temperature dependence of the pitch of the cholesteric helix of poly(γ‐benzyl‐L‐glutamate) in N,N‐dimethylformamide and N‐methyl‐2‐pyrrolidone

AbstractTemperature depenences of the pitch of cholesteric helix in solutions of poly(y‐benzyl‐L‐glutamate) in N,N‐dimethylformamide and N‐methyl‐2‐pyrrolidone were measured for various molar masses of poly(γ‐benzyl‐L‐glutamate). It was found that in N‐methyl‐2‐pyrrolidone inversion of the cholesteric helix takes place, i. e., that the right‐handed helix changes to the lefthanded one. By using an equation derived by Kimura, the temperatures at which the system has a nematic order were determined. The results obtained allow the statement that an important role in the inversion of the cholesteric helix in poly(γ‐benzyl‐L‐glutamate) solutions is played by conformational changes in side chains of the polypeptide molecule.

Unique poly(dA).poly(dT) B'-conformation in cellular and synthetic DNAs.

Poly(dA).poly(dT), but not B-form DNA, is specifically recognized by experimentally induced anti-kinetoplast or anti-poly(dA).poly(dT) immunoglobulins. Antibody binding is completely competed by poly(dA).poly(dT) and poly(dA).poly(dU) but not by other single- or double-stranded DNA sequences in a right-handed B-form. Antibody interaction with poly(dA).poly(dT) depends on immunoglobulin concentration, incubation time and temperature, and is sensitive to elevated ionic strengths. Similar conformations, for example, (dA)4-6 X (dT)4-6, in the kinetoplast DNA of the parasite Leishmania tarentolae are also immunogenic and induce specific anti-poly(dA).poly(dT) antibodies. These antibody probes specifically recognize nuclear and kinetoplast DNA in fixed flagellated kinetoplastid cells as evidenced by immunofluorescence microscopy. Anti-poly(dA).poly(dT) immunofluorescence is DNase-sensitive and competed by poly(dA).poly(dT), but not other classical double-stranded B-DNAs. Thus, these unique cellular B'-DNA helices are immunogenic and structurally similar to synthetic poly(dA).poly(dT) helices in solution.

Structure and Dynamics of Double Helices in Solution: Modes of DNA Bending

The long range structure of DNA restriction fragments has been analysed by electro-optical measurements. The overall rotation time constants observed in a low salt buffer with monovalent ions is shown to decrease upon addition of Mg2+ or spermine. Since the circular dichroism and also the limiting value of the linear dichroism remain almost constant under these conditions, the effect is attributed to a change of the long range structure. According to a weakly bending rod model, the persistence length decreases from about 600 A in the absence of Mg2+ or spermine to about 350 A in the presence of these ions. The persistence length measured in the presence of Mg2+ is almost independent of temperature in the range of 10 to 40 degrees C. The nature of DNA bending is analysed by measurements of bending amplitudes and time constants from dichroism decay curves. The observed absence of changes in the bending amplitudes upon addition of Mg2+ or spermine, even though addition induces changes of the persistence length by a factor of 2, is hardly consistent with simple thermal bending. The combined results, including the remarkably small temperature dependence of persistence length and bending amplitude, can be explained by the existence of two bending effects: inherent curvature of DNA dominates at low temperature, whereas thermal bending prevails at high temperature. Analysis of bending amplitudes from dichroism decay curves according to an arc model provides an approximate measure for the degree of bending in restriction fragments. The model is consistent with the observed chain length dependence of bending amplitudes and provides an approximate curvature corresponding to a radius of about 400 A. Thus the curvature observed in restriction fragments is similar to that observed for high molecular DNA condensed into toroids by addition of ions like spermine. Particularly strong bending of DNA is induced by [Co(NH3)6]3+, indicated by an apparent persistence length of 200 A and an increased bending amplitude together with a reduced limit value of the linear dichroism. This effect is attributed to the high charge density of this ion and potential site binding.