Interaction of the histone (H3-H4)2 tetramer of the nucleosome with positively supercoiled DNA minicircles: Potential flipping of the protein from a left- to a right-handed superhelical form.

We have studied the ability of the histone (H3-H4)2 tetramer, the central part of the nucleosome of eukaryotic chromatin, to form particles on DNA minicircles of negative and positive superhelicities, and the effect of relaxing these particles with topoisomerase I. The results show that even modest positive torsional stress from the DNA, and in particular that generated by DNA thermal fluctuations, can trigger a major, reversible change in the conformation of the particle. Neither a large excess of naked DNA, nor a crosslink between the two H3s prevented the transition from one form to the other. This suggested that during the transition, the histones neither dissociated from the DNA nor were even significantly reshuffled. Moreover, the particles reconstituted on negatively and positively supercoiled minicircles look similar under electron microscopy. These data agree best with a transition involving a switch of the wrapped DNA from a left- to a right-handed superhelix. It is further proposed, based on the left-handed overall superhelical conformation of the tetramer within the octamer [Arents, G., Burlingame, R. W., Wang, B. C., Love, W. E. & Moudrianakis, E. N. (1991) Proc. Natl.Acad. Sci. USA 88, 10148-10152] that this change in DNA topology is mediated by a similar change in the topology of the tetramer itself, which may occur through a rotation (or a localized deformation) of the two H3-H4 dimers about their H3-H3 interface. Potential implications of this model for nucleosome dynamics in vivo are discussed.

The conducting form of gramicidin A is a right-handed double-stranded double helix

The linear pentadecapeptide antibiotic, gramicidin D, is a naturally occurring product of Bacillus brevis known to form ion channels in synthetic and natural membranes. The x-ray crystal structures of the right-handed double-stranded double-helical dimers (DSDHℛ) reported here agree with 15N-NMR and CD data on the functional gramicidin D channel in lipid bilayers. These structures demonstrate single-file ion transfer through the channels. The results also indicate that previous crystal structure reports of a left-handed double-stranded double-helical dimer in complex with Cs+ and K+ salts may be in error and that our evidence points to the DSDHℛ as the major conformer responsible for ion transport in membranes.

A Z-DNA binding domain present in the human editing enzyme, double-stranded RNA adenosine deaminase

Editing of RNA changes the read-out of information from DNA by altering the nucleotide sequence of a transcript. One type of RNA editing found in all metazoans uses double-stranded RNA (dsRNA) as a substrate and results in the deamination of adenosine to give inosine, which is translated as guanosine. Editing thus allows variant proteins to be produced from a single pre-mRNA. A mechanism by which dsRNA substrates form is through pairing of intronic and exonic sequences before the removal of noncoding sequences by splicing. Here we report that the RNA editing enzyme, human dsRNA adenosine deaminase (DRADA1, or ADAR1) contains a domain (Zα) that binds specifically to the left-handed Z-DNA conformation with high affinity (KD = 4 nM). As formation of Z-DNA in vivo occurs 5′ to, or behind, a moving RNA polymerase during transcription, recognition of Z-DNA by DRADA1 provides a plausible mechanism by which DRADA1 can be targeted to a nascent RNA so that editing occurs before splicing. Analysis of sequences related to Zα has allowed identification of motifs common to this class of nucleic acid binding domain.

Direct interaction of flagellin termini essential for polymorphic ability of flagellar filament

We report the structures of flagellar filaments reconstituted from various flagellins with small terminal truncations. Flagellins from Salmonella typhimurium strains SJW1103 (wild type), SJW1660, and SJW1655 were used, which form a left-handed supercoil, the L- and R-type straight forms, respectively. Structure analyses were done by electron cryomicroscopy and helical image reconstruction with a help of x-ray fiber diffraction for determining precise helical symmetries. Truncation of either terminal region, irrespective of the original flagellin species, results in a straight filament having a helical symmetry distinct either from the L- or R-type. This filament structure is named Lt-type. Although the local subunit packing is similar in all three types, a close comparison shows that the Lt-type packing is almost identical to the R-type but distinct from the L-type, which demonstrates the strong two-state preference of the subunit interactions. The structure clearly suggests that both termini are located in the inner tube of the concentric double-tubular structure of the filament core, and their proper interaction is responsible for the correct folding of fairly large terminal regions that form the inner tube. The double tubular structure appears to be essential for the polymorphic ability of flagellar filaments, which is required for the swimming–tumbling of bacterial taxis.

Field theory in superfluid 3He: What are the lessons for particle physics, gravity, and high-temperature superconductivity?

There are several classes of homogeneous Fermi systems that are characterized by the topology of the energy spectrum of fermionic quasiparticles: (i) gapless systems with a Fermi surface, (ii) systems with a gap in their spectrum, (iii) gapless systems with topologically stable point nodes (Fermi points), and (iv) gapless systems with topologically unstable lines of nodes (Fermi lines). Superfluid 3He-A and electroweak vacuum belong to the universality class 3. The fermionic quasiparticles (particles) in this class are chiral: they are left-handed or right-handed. The collective bosonic modes of systems of class 3 are the effective gauge and gravitational fields. The great advantage of superfluid 3He-A is that we can perform experiments by using this condensed matter and thereby simulate many phenomena in high energy physics, including axial anomaly, baryoproduction, and magnetogenesis. 3He-A textures induce a nontrivial effective metrics of the space, where the free quasiparticles move along geodesics. With 3He-A one can simulate event horizons, Hawking radiation, rotating vacuum, etc. High-temperature superconductors are believed to belong to class 4. They have gapless fermionic quasiparticles with a “relativistic” spectrum close to gap nodes, which allows application of ideas developed for superfluid 3He-A.

Functional activation in motor cortex reflects the direction and the degree of handedness

Handedness is the clearest example of behavioral lateralization in humans. It is not known whether the obvious asymmetry manifested by hand preference is associated with similar asymmetry in brain activation during movement. We examined the functional activation in cortical motor areas during movement of the dominant and nondominant hand in groups of right-handed and left-handed subjects and found that use of the dominant hand was associated with a greater volume of activation in the contralateral motor cortex. Furthermore, there was a separate relation between the degree of handedness and the extent of functional lateralization in the motor cortex. The patterns of functional activation associated with the direction and degree of handedness suggest that these aspects are independent and are coded separately in the brain.

Symmetries in bacterial motility

Descriptions are given of three kinds of symmetries encountered in studies of bacterial locomotion, and of the ways in which they are circumvented or broken. A bacterium swims at very low Reynolds number: it cannot propel itself using reciprocal motion (by moving through a sequence of shapes, first forward and then in reverse); cyclic motion is required. A common solution is rotation of a helical filament, either right- or left-handed. The flagellar rotary motor that drives each filament generates the same torque whether spinning clockwise or counterclockwise. This symmetry is broken by coupling to the filament. Finally, bacterial populations, grown in a nutrient medium from an inoculum placed at a single point, usually move outward in symmetric circular rings. Under certain conditions, the cells excrete a chemoattractant, and the rings break up into discrete aggregates that can display remarkable geometric order.

Retro and retroenantio analogs of cecropin-melittin hybrids.

Hybrid analogs of cecropin A (CA) and melittin (M), which are potent antibacterial peptides, have been synthesized. To understand the structural requirements for this antibacterial activity, we have also synthesized the enantio, retro, and retroenantio isomers of two of the hybrids and their N-terminally acetylated derivatives. All analogs of CA(1-13)M(1-13)-NH2 were as active as the parent peptide against five test bacterial strains, but one bacterial strain was resistant to the retro and retroenantio derivatives. Similarly, all analogs of CA(1-7)M(2-9)-NH2 were active against four strains, while two strains were resistant to the retro and retroenantio analogs containing free NH3+ end groups, but acetylation restored activity against one of them. From these data it was concluded that chirality of the peptide was not a critical feature, and full activity could be achieved with peptides containing either all L- or all D-amino acids in their respective right-handed or left-handed helical conformations. For most of the bacterial strains, the sequence of these peptides or the direction of the peptide bonds could be critical but not both at the same time. For some strains, both needed to be conserved.