Recently in Crystallography Category

In a single cell, thousands of simultaneously occurring biochemical reactions carry out such functions as converting and storing energy and regulating nutrient levels; together, those processes make up the cell’s metabolic network. Computational biology involves, among other things, the linking of metabolic pathways to form a metabolic network model, a promising tool for preclinical drug studies and other medical research. However, such computational models do not traditionally include the function-determining structural details of a network’s macromolecules; for example, an enzyme’s ability to catalyze reactions and regulate the cell’s response to external stimuli is determined by its three-dimensional configuration. Now, an international team led by Adam Godzik at the Burnham Institute for Medical Research in California has taken a rare step and introduced atomic-level protein structural data to the metabolic network model of an ancient thermophilic bacterium, Thermotoga maritima, shown in this optical microscope image. The image also shows schematics of proteins in their 3D configurations, which, when they were expressed in the reconstructed metabolic network, helped the research team solve the puzzle of how proteins evolve when their cell networks grow larger.

It turns out that only 37% of T. maritima’s proteins are essential to the formation of its metabolic network; those “core-essential” proteins adopt the bulk—61%—of the bacterium’s relatively few unique 3D configurations. The finding suggests that the core-essential proteins evolved their structure to perform additional functions in distinct pathways. (Y. Zhang et al., Science 325, 1544, 2009.)—Jermey N.A. Matthews

Concrete is the most prevalent synthetic material on Earth, yet the detailed nature of its primary binding constituent, hydrated cement, is only poorly understood. When cement, a dry powder that consists mostly of calcium oxide and silicate, is mixed with water, the material hardens through the formation of a complex hydrated oxide called calcium-silicate-hydrate. But the microscopic structure of C-S-H is largely unknown—even its stoichiometry, as suggested by convention with hyphens. C-S-H's structure had been thought to be related to that of two naturally occurring calcium silicate minerals, but those minerals can't explain C-S-H's observed properties. Armed with recent measurements of C-S-H's density and its ratio of calcium to silicon atoms, a team of researchers at MIT has proposed a new molecular model for C-S-H based on atom-scale simulations: Layers of calcium ions (gray in the figure) are surrounded by silicon (yellow) and oxygen (red) arranged as short silica chains one, two, and five units long; between those layers are water (oxygen in blue, hydrogen in white) and interlayer calcium ions (green) that ensure overall neutrality. The model's chemical composition, (CaO)_1.65(SiO₂)(H₂O)_1.75, agrees well with results from neutron scattering experiments. In addition to reproducing the known structural properties of the material, the model also suggests that at short length scales C-S-H should be viewed as a glassy phase. With an atom-level model of the C-S-H structure now in hand, the researchers hope to be able to manipulate the macroscopic properties of concrete, such as its strength and temperature resistance. (R. J.-M. Pellenq et al., Proc. Natl. Acad. Sci. USA, doi:10.1073/pnas.0902180106, in press.)—Richard J. Fitzgerald

Dispersed in the brains of Alzheimer's patients are disk-shaped lesions, about 100 µm across. Whether those lesions, or plaques, are a cause or a consequence of Alzheimer's disease is controversial, but their composition is clear. The plaques are made from fibrous aggregates—amyloid—of protein or their shorter cousins, peptides. Once sequestered in amyloid, a protein or a peptide can no longer perform its function. Even if amyloid does not directly cause Alzheimer's and other diseases, it seems at best a useless, dead-end repository of proteinaceous material. But as a new paper exemplifies, a less malign view of amyloid is emerging. Roland Riek of ETH Zürich and his collaborators have demonstrated that our bodies exploit amyloid as a temporary storage medium for a wide range of peptide hormones. Riek suspected a hormone–amyloid connection when he found that a stress hormone formed amyloid fibrils. He and his collaborators then subjected 41 other peptide hormones to a battery of biochemical, biophysical, and crystallographic tests. The finding: 75% of the peptide hormones form amyloid; and, as befits a storage medium, the amyloid can also disaggregate to release the peptides. In a final test, the team stained slices of mouse brain with hormone-sensitive and amyloid-sensitive dyes. The stained regions coincided. Riek's discovery adds to the modest but growing list of examples of so-called functional amyloid that perform useful tasks in living organisms. Evidently, amyloid is not always pernicious. (S. K. Maji et al., Science 325, 328, 2009.)—Charles Day