Showing papers by "Sebastian Doniach published in 2008"

Long single α-helical tail domains bridge the gap between structure and function of myosin VI

Abstract: Myosin VI has challenged the lever arm hypothesis of myosin movement because of its ability to take ~36-nm steps along actin with a canonical lever arm that seems to be too short to allow such large steps. Here we demonstrate that the large step of dimeric myosin VI is primarily made possible by a medial tail in each monomer that forms a rare single α-helix of ~10 nm, which is anchored to the calmodulin-bound IQ domain by a globular proximal tail. With the medial tail contributing to the ~36-nm step, rather than dimerizing as previously proposed, we show that the cargo binding domain is the dimerization interface. Furthermore, the cargo binding domain seems to be folded back in the presence of the catalytic head, constituting a potential regulatory mechanism that inhibits dimerization.

Dynamic charge interactions create surprising rigidity in the ER/K α-helical protein motif

Abstract: Protein α-helices are ubiquitous secondary structural elements, seldom considered to be stable without tertiary contacts However, amino acid sequences in proteins that are based on alternating repeats of four glutamic acid (E) residues and four positively charged residues, a combination of arginine (R) and lysine (K), have been shown to form stable α-helices in a few proteins, in the absence of tertiary interactions Here, we find that this ER/K motif is more prevalent than previously reported, being represented in proteins of diverse function from archaea to humans By using molecular dynamics (MD) simulations, we characterize a dynamic pattern of side-chain interactions that extends along the backbone of ER/K α-helices A simplified model predicts that side-chain interactions alone contribute substantial bending rigidity (05 pN/nm) to ER/K α-helices Results of small-angle x-ray scattering (SAXS) and single-molecule optical-trap analyses are consistent with the high bending rigidity predicted by our model Thus, the ER/K α-helix is an isolated secondary structural element that can efficiently span long distances in proteins, making it a promising tool in designing synthetic proteins We propose that the significant rigidity of the ER/K α-helix can help regulate protein function, as a force transducer between protein subdomains

Critical assessment of nucleic acid electrostatics via experimental and computational investigation of an unfolded state ensemble.

Abstract: Electrostatic forces, acting between helices and modulated by the presence of the ion atmosphere, are key determinants in the energetic balance that governs RNA folding. Previous studies have employed Poisson−Boltzmann (PB) theory to compute the energetic contribution of these forces in RNA folding. However, the complex interaction of these electrostatic forces with RNA features such as tertiary contact formation, specific ion-binding, and complex interhelical junctions present in prior studies precluded a rigorous evaluation of PB theory, especially in physiologically important Mg2+ solutions. To critically assess PB theory, we developed a model system that isolates these electrostatic forces. The model system, composed of two DNA duplexes tethered by a polyethylene glycol junction, is an analog for the unfolded state of canonical helix-junction-helix motifs found in virtually all structured RNAs. This model system lacks the complicating features that have precluded a critical assessment of PB in prior s...

Association of partially-folded intermediates of staphylococcal nuclease induces structure and stability.

Abstract: Staphylococcal nuclease forms three different partially-folded intermediates at low pH in the presence of low to moderate concentration of anions, differing in the amount of secondary structure, globularity, stability, and compactness. Although these intermediates are monomeric at low protein concentration (< or =0.25 mg/mL), increasing concentrations of protein result in the formation of dimers and soluble oligomers, ultimately leading to larger insoluble aggregates. Unexpectedly, increasing protein concentration not only led to association, but also to increased structure of the intermediates. The secondary structure, stability, and globularity of the two less-ordered partially-folded intermediates (A1 and A2) were substantially increased upon association, suggesting that aggregation induces structure. An excellent correlation was found between degree of association and amount of structure measured by different techniques, including circular dichroism, fluorescence, Fourier transform infrared spectroscopy (FTIR), and small-angle X-ray scattering. The associated states were also substantially more stable toward urea denaturation than the monomeric forms. A mechanism is proposed, in which the observed association of monomeric intermediates involves intermolecular interactions which correspond to those found intramolecularly in normal folding to the native state.

Self-consistent solution for proximity effect and Josephson current in ballistic graphene SNS Josephson junctions

Abstract: We use a tight-binding Bogoliubov-de Gennes (BdG) formalism to self-consistently calculate the proximity effect, Josephson current, and local density of states in ballistic graphene SNS Josephson junctions. Both short and long junctions, with respect to the superconducting coherence length, are considered, as well as different doping levels of the graphene. We show that self-consistency does not notably change the current-phase relationship derived earlier for short junctions using the non-selfconsistent Dirac-BdG formalism but predict a significantly increased critical current with a stronger junction length dependence. In addition, we show that in junctions with no Fermi level mismatch between the N and S regions superconductivity persists even in the longest junctions we can investigate, indicating a diverging Ginzburg-Landau superconducting coherence length in the normal region.

The effect of electronic correlations on Josephson current and proximity effect in SNS graphene junctions

Abstract: Submitted for the MAR08 Meeting of The American Physical Society The effect of electronic correlations on Josephson current and proximity effect in SNS graphene junctions ANNICA BLACK-SCHAFFER, SEBASTIAN DONIACH, Stanford University — Using the self-consistent tightbinding Bogoliubov-de Gennes (BdG) formalism, we investigate the proximity effect and current-phase relationship in SNS graphene Josephson junctions. Both short and long junctions are considered, as well as different doping levels of the graphene. For short junctions at zero doping in the uncorrelated regime our results agree with those found using the non self-consistent Dirac-BdG formalism [1]. We introduce electronic correlations in the Hamiltonian by including the intrinsic nearest-neighbor spin-singlet coupling present in pπ-bonded planar organic molecules. We study the possibility of coupling this intrinsic sor d-wave superconducting pairing [2] to the extrinsic s-wave order parameter induced by the metal electrodes. The intrinsic dwave solution, favored in doped graphene, appears for longer doped junctions. For short junctions, the s-wave solution can occur, although the result is sensitive to the type of interface. We also report on the two different intrinsic superconducting states’ influence on the supercurrent. [1] M. Titov et al. PRB 74 041401 (2006) [2] A. Black-Schaffer et al. PRB 75 134512 (2007) Annica Black-Schaffer Stanford University Date submitted: 26 Nov 2007 Electronic form version 1.4