In situ Alphavirus Assembly and Budding Mechanism Revealed by Cellular CryoET

Chikungunya virus (CHIKV) is a representative alphavirus causing debilitating arthritogenic disease in humans. Alphavirus particles assemble into two icosahedral protein layers: the glycoprotein spike shell embedded in a lipid envelope and the inner nucleocapsid (NC) core. In contrast to matrix-driven assembly of some enveloped viruses, the assembly/budding process of two-layered icosahedral particles remains poorly understood. Here we used cryogenic electron tomography (cryoET) to capture snapshots of the CHIKV assembly process in infected human cells. Subvolume classification of the snapshots revealed 12 intermediate structures, representing different stages of assembly/budding at the plasma membrane. Further subtomogram average structures ranging from subnanometer to nanometer resolutions show that immature, non-icosahedral NCs function as rough scaffolds to trigger icosahedral assembly of the glycoprotein spike lattice, which in turn progressively transforms the underlying NCs into icosahedral cores during budding. Here we resolve a long-standing mechanistic question about the role of spikes and NCs in assembly of two-layered icosahedral shells. Further, data of CHIKV-infected cells treated with budding-inhibiting antibodies shows that spacing spikes apart to prevent their lateral interactions prevents the plasma membrane bending around NC cores, thus blocking virus budding. These findings provide the molecular details of icosahedral enveloped virus formation and antibodies against assembly/budding.

Tuneable local order in thermoelectric crystals

Although crystalline solids are characterized by their periodic structures, some are only periodic on average and deviate on a local scale. Such disordered crystals with distinct local structures have unique properties arising from both collective and localized behaviour. Different local orderings can exist with identical average structures, making their differences hidden to Bragg diffraction methods. Using high-quality single-crystal X-ray diffuse scattering the local order in thermoelectric half-Heusler Nb1−x CoSb is investigated, for which different local orderings are observed. It is shown that the vacancy distribution follows a vacancy repulsion model and the crystal composition is found always to be close to x = 1/6 irrespective of nominal sample composition. However, the specific synthesis method controls the local order and thereby the thermoelectric properties thus providing a new frontier for tuning material properties.

Linear and bent triatomic molecules are not qualitatively different!

I, and other authors, have discussed in several recent publications that “linear” triatomic molecules (defined as having linear equilibrium structures) are necessarily observed as being bent on ro-vibrational average. We have demonstrated this theoretically by calculations of the rotation–vibration expectation values, [Formula: see text], where [Formula: see text] is the bond angle supplement, [Formula: see text] being the instantaneous value of the bond angle of the triatomic molecule A–B–C. Direct experimental evidence of bent average structures has been obtained by other authors in Coulomb explosion imaging experiments, and indirect evidence from re-interpretation of experimentally derived rotational constant values. In spite of a rather significant amount of evidence in support of the bent average structures, the idea has been heavily criticized. In the present work I discuss in more detail some of the arguments for the bent average structures put forward in previous papers, and I hope to correct and clarify some of the misunderstandings leading to the criticisms. Part of the criticism originates in a widespread, but fallacious, belief among spectroscopists that linear and bent chain molecules have qualitatively different energy-level and spectral intensity patterns. This is not true. One can view the linear-molecule energy level and spectral patterns as limiting cases of the bent-molecule ones.

The Asphaltene Fraction – Demystified

The asphaltene constituents of crude oil are the highest molecular weight heaviest and most polar constituents in the oil and the fraction is isolated a dark brown to black friable solids that have no definite melting point and usually foam and swell on heating to leave a carbonaceous residue. The fraction is obtained from crude oil by the addition of a hydrocarbon liquid (such as n-pentane or n-heptane). Any molecular models derived for asphaltene constituents must be in keeping with behavioral characteristics. Efforts have been (and continue to be) made without justification to describe the asphaltene fraction in terms of a single, representative asphaltene molecule or molecules incorporating, in the correct proportions, all of the chemical constituents known to be present in a given asphaltenic matrix. Obviously, the chemistry and structural features of the constituents of crude oil asphaltene fractions will be dictated by the distribution of functional and structural type that occur in the fraction. This makes the representation of the structure and functionality of the constituents by so-called average structures very difficult (if not, impossible) to conceive.

Do available protein 3D structures reflect human genetic and functional diversity?

ABSTRACTGenomic databases are substantially biased towards European ancestry populations, and this bias contributes to health disparities. Here, we quantify how well 66,971 experimentally characterized human protein 3D structures represent the diversity of protein sequences observed across the 1000 Genomes Project. More than 85% of available structures do not match a sequence observed in at least one individual, and on average structures match the sequence of 74% of individuals. Nearly 23% of human structures do not match any observed sequences; however, after masking engineered/known mutations, this decreases to ~4%. African ancestry sequences are modestly, but significantly, less likely to be represented by structures (73.5% vs. 74.0%). These differences are mainly driven by the greater genetic diversity of African populations. We identify thousands of variants unrepresented in available structures that influence protein structure and function. Thus, the use of a single structure as representative of “the wild type” protein will often bias results against many individuals. The diversity of protein sequence and structure must be considered to enable accurate, reproducible, and generalizable conclusions from structural analyses.

Structure modulations in nonlinear optical (NLO) materials Cs2TB4O9(T= Ge, Si)

Incommensurately modulated borate structures of a new type were studied in detail in the nonlinear optical (NLO) materials Cs2TB4O9(T= Ge, Si) using single-crystal X-ray diffraction techniques. The structures were solved by the charge-flipping algorithm in the superspace groupI2(αβ0)0. The refinement results strongly suggest that the main structure modulation feature of Cs2TB4O9is the ordering of the O atoms. With these modulated structure models, the unreasonable B—O distances in the average structures were explained as the ordering of BO4and BO3.

Periodic average structures of colloidal quasicrystals

Observation of periodic average structure of a colloidal monolayer subjected to a one-dimensional quasiperiodic laser potential.