Microscopic Theory of Protein Folding Rates.I: Fine Structure of the Free Energy Profile and Folding Routes from a Variational Approach

A microscopic theory of the free energy barriers and folding routes for minimally frustrated proteins is presented, greatly expanding on the presentation of the variational approach outlined previously [J. J. Portman, S. Takada, P. G. Wolynes, Phys. Rev. Lett. {\bf 81}, 5237 (1998)]. We choose the $\lambda$-repressor protein as an illustrative example and focus on how the polymer chain statistics influence free energy profiles and partially ordered ensembles of structures. In particular, we investigate the role of chain stiffness on the free energy profile and folding routes. We evaluate the applicability of simpler approximations in which the conformations of the protein molecule along the folding route are restricted to have residues that are either entirely folded or unfolded in contiguous stretches. We find that the folding routes obtained from only one contiguous folded region corresponds to a chain with a much greater persistence length than appropriate for natural protein chains, while the folding route obtained from two contiguous folded regions is able to capture the relatively folded regions calculated within the variational approach. The free energy profiles obtained from the contiguous sequence approximations have larger barriers than the more microscopic variational theory which is understood as a consequence of partial ordering.Comment: 16 pages, 11 figure

Sulphur abundances in metal-poor stars

We investigate the debated "sulphur discrepancy" found among metal-poor stars of the Galactic halo with [Fe/H] < -2. This discrepancy stems in part from the use of two different sets of sulphur lines, the very weak triplet at 8694-95 A and the stronger triplet lines at 9212 - 9237 A. For three representative cases of metal-poor dwarf, turnoff and subgiant stars, we argue that the abundances from the 8694-95 lines have been overestimated which has led to a continually rising trend of [S/Fe] as metallicity decreases. Given that the near-IR region is subject to CCD fringing, these weak lines become excessively difficult to measure accurately in the metallicity regime of [Fe/H] < -2. Based on homogeneously determined spectroscopic stellar parameters, we also present updated [S/Fe] ratios from the 9212-9237 lines which suggest a plateau-like behaviour similar to that seen for other alpha elements.Comment: accepted by A&A, 4 pages, 3 tables, 1 figure; v2: Table2 updated with metallicities from other work

A point mutation of integrin beta 1 subunit blocks binding of alpha 5 beta 1 to fibronectin and invasin but not recruitment to adhesion plaques.

A point mutation in a highly conserved region of the beta 1 subunit, Asp130 to Ala (D130A) substitution, abrogates the Arg-Gly-Asp (RGD)-dependent binding of alpha 5 beta 1 to fibronectin (FN) without disrupting gross structure or heterodimer assembly. The D130A mutation also interferes with binding to invasin, a ligand that lacks RGD sequence. In spite of the lack of detectable FN binding by alpha 5 beta 1(D130A), it was recruited to adhesion plaques formed on FN by endogenous hamster receptors. Thus, intact ligand binding function is not required for recruitment of alpha 5 beta 1 to adhesion plaques. Overexpression of beta 1(D130A) partially interfered with endogenous alpha 5 beta 1 function, thus defining a dominant negative beta 1 integrin mutation

Microscopic Theory of Protein Folding Rates.II: Local Reaction Coordinates and Chain Dynamics

The motion involved in barrier crossing for protein folding are investigated in terms of the chain dynamics of the polymer backbone, completing the microscopic description of protein folding presented in the previous paper. Local reaction coordinates are identified as collective growth modes of the unstable fluctuations about the saddle-points in the free energy surface. The description of the chain dynamics incorporates internal friction (independent of the solvent viscosity) arising from the elementary isomerizations of the backbone dihedral angles. We find that the folding rate depends linearly on the solvent friction for high viscosity, but saturates at low viscosity because of internal friction. For $\lambda$-repressor, the calculated folding rate prefactor, along with the free energy barrier from the variational theory, gives a folding rate that agrees well with the experimentally determined rate under highly stabilizing conditions, but the theory predicts too large a folding rate at the transition midpoint. This discrepancy obtained using a fairly complete quantitative theory inspires a new set of questions about chain dynamics, specifically detailed motions in individual contact formation.Comment: 18 pages, 8 figure

The infrared conductivity of Nax_xCoO2_2: evidence of gapped states

We present infrared ab-plane conductivity data for the layered cobaltate Na$_x$CoO$_2$ at three different doping levels ($x=0.25, 0.50$, and 0.75). The Drude weight increases monotonically with hole doping, $1-x$. At the lowest hole doping level $x$=0.75 the system resembles the normal state of underdoped cuprate superconductors with a scattering rate that varies linearly with frequency and temperature and there is an onset of scattering by a bosonic mode at 600 \cm. Two higher hole doped samples ($x=0.50$ and 0.25) show two different-size gaps (110 \cm and 200 \cm, respectively) in the optical conductivities at low temperatures and become insulators. The spectral weights lost in the gap region of 0.50 and 0.25 samples are shifted to prominent peaks at 200 \cm and 800 \cm, respectively. We propose that the two gapped states of the two higher hole doped samples ($x$=0.50 and 0.25) are pinned charge ordered states.Comment: 4 pages, 3 figure

Distinct functions of integrin alpha and beta subunit cytoplasmic domains in cell spreading and formation of focal adhesions.

Integrin-mediated cell adhesion often results in cell spreading and the formation of focal adhesions. We exploited the capacity of recombinant human alpha IIb beta 3 integrin to endow heterologous cells with the ability to adhere and spread on fibrinogen to study the role of integrin cytoplasmic domains in initiation of cell spreading and focal adhesions. The same constructs were also used to analyze the role of the cytoplasmic domains in maintenance of the fidelity of the integrin repertoire at focal adhesions. Truncation mutants of the cytoplasmic domain of alpha IIb did not interfere with the ability of alpha IIb beta 3 to initiate cell spreading and form focal adhesions. Nevertheless, deletion of the alpha IIb cytoplasmic domain allowed indiscriminate recruitment of alpha IIb beta 3 to focal adhesions formed by other integrins. Truncation of the beta 3 subunit cytoplasmic domain abolished cell spreading mediated by alpha IIb beta 3 and also abrogated recruitment of alpha IIb beta 3 to focal adhesions. This truncation also dramatically impaired the ability of alpha IIb beta 3 to mediate the contraction of fibrin gels. In contrast, the beta 3 subunit cytoplasmic truncation did not reduce the fibrinogen binding affinity of alpha IIb beta 3. Thus, the integrin beta 3 subunit cytoplasmic domain is necessary and sufficient for initiation of cell spreading and focal adhesion formation. Further, the beta 3 cytoplasmic domain is required for the transmission of intracellular contractile forces to fibrin gels. The alpha subunit cytoplasmic domain maintains the fidelity of recruitment of the integrins to focal adhesions and thus regulates their repertoire of integrins

Halo-Galaxy Lensing: A Full Sky Approach

The halo-galaxy lensing correlation function or the average tangential shear profile over sampled halos is a very powerful means of measuring the halo masses, the mass profile, and the halo-mass correlation function of very large separations in the linear regime. We reformulate the halo-galaxy lensing correlation in harmonic space. We find that, counter-intuitively, errors in the conventionally used flat-sky approximation remain at a % level even at very small angles. The errors increase at larger angles and for lensing halos at lower redshifts: the effect is at a few % level at the baryonic acoustic oscillation scales for lensing halos of $z\sim 0.2$, and comparable with the effect of primordial non-Gaussianity with $f_{\rm NL}\sim 10$ at large separations. Our results allow to readily estimate/correct for the full-sky effect on a high-precision measurement of the average shear profile available from upcoming wide-area lensing surveys.Comment: 12 pages, 4 figure

Electronic Collective Modes and Superconductivity in Layered Conductors

A distinctive feature of layered conductors is the presence of low-energy electronic collective modes of the conduction electrons. This affects the dynamic screening properties of the Coulomb interaction in a layered material. We study the consequences of the existence of these collective modes for superconductivity. General equations for the superconducting order parameter are derived within the strong-coupling phonon-plasmon scheme that account for the screened Coulomb interaction. Specifically, we calculate the superconducting critical temperature Tc taking into account the full temperature, frequency and wave-vector dependence of the dielectric function. We show that low-energy plasmons may contribute constructively to superconductivity. Three classes of layered superconductors are discussed within our model: metal-intercalated halide nitrides, layered organic materials and high-Tc oxides. In particular, we demonstrate that the plasmon contribution (electronic mechanism) is dominant in the first class of layered materials. The theory shows that the description of so-called ``quasi-two-dimensional superconductors'' cannot be reduced to a purely 2D model, as commonly assumed. While the transport properties are strongly anisotropic, it remains essential to take into account the screened interlayer Coulomb interaction to describe the superconducting state of layered materials.Comment: Final version (minor changes) 14 pages, 6 figure