Phenylalanine tRNA showing the anticodon (yellow) and the amino acid, phenylalanine (blue and red spheres).

Structural biologists create crystals of proteins, shown here, as a first step in a process called X-ray crystallography, which can reveal detailed, three-dimensional protein structures.

A crystal of pig trypsin protein created for X-ray crystallography, which can reveal detailed, three-dimensional protein structures.

Some children are born with a mutation in a regulatory site on this enzyme that causes them to over-secrete insulin when they consume protein. We found that a compound from green tea (shown in the stick figure and by the yellow spheres on the enzyme) is able to block this hyperactivity when given to animals with this disorder.

In the top snapshots, the brain of a sleep-deprived fruit fly glows orange, marking high concentrations of a synaptic protein called Bruchpilot (BRP) involved in communication between neurons. The color particularly lights up brain areas associated with learning. By contrast, the bottom images from a well-rested fly show lower levels of the protein. These pictures illustrate the results of an April 2009 study showing that sleep reduces the protein's levels, suggesting that such "downscaling" resets the brain to normal levels of synaptic activity and makes it ready to learn after a restful night.

This video shows the structure of the pore-forming protein VDAC-1 from humans. This molecule mediates the flow of products needed for metabolism--in particular the export of ATP--across the outer membrane of mitochondria, the power plants for eukaryotic cells. VDAC-1 is involved in metabolism and the self-destruction of cells--two biological processes central to health.

Related to videos 2571 and 2572.

Model based on X-ray crystallography of the structure of a small heat shock protein complex from the bacteria, Methanococcus jannaschii. Methanococcus jannaschii is an organism that lives at near boiling temperature, and this protein complex helps it cope with the stress of high temperature. Similar complexes are produced in human cells when they are "stressed" by events such as burns, heart attacks, or strokes. The complexes help cells recover from the stressful event.

The proteasome is a critical multiprotein complex in the cell that breaks down and recycles proteins that have become damaged or are no longer needed. This movie shows how a protein substrate (red) is bound through its ubiquitin chain (blue) to one of the ubiquitin receptors of the proteasome (Rpn10, yellow). The substrate's flexible engagement region then gets engaged by the AAA+ motor of the proteasome (cyan), which initiates mechanical pulling, unfolding and movement of the protein into the proteasome's interior for cleavage into shorter protein pieces called peptides. During movement of the substrate, its ubiquitin modification gets cleaved off by the deubiquitinase Rpn11 (green), which sits directly above the entrance to the AAA+ motor pore and acts as a gatekeeper to ensure efficient ubiquitin removal, a prerequisite for fast protein breakdown by the 26S proteasome. Related to image 3763.

The human genome contains much of the information needed for every cell in the body to function. However, different types of cells often need different types of information. Access to DNA is controlled, in part, by how tightly it’s wrapped around proteins called histones to form nucleosomes. The complex shown here, from yeast cells (PDB entry 6Z6P), includes several histone deacetylase (HDAC) enzymes (green and blue) bound to a nucleosome (histone proteins in red; DNA in yellow). The yeast HDAC enzymes are similar to the human enzymes. Two enzymes form a V-shaped clamp (green) that holds the other others, a dimer of the Hda1 enzymes (blue). In this assembly, Hda1 is activated and positioned to remove acetyl groups from histone tails.

A 360-degree view of the molecule himastatin, which was first isolated from the bacterium Streptomyces himastatinicus. Himastatin shows antibiotic activity. The researchers who created this video developed a new, more concise way to synthesize himastatin so it can be studied more easily.

More information about the research that produced this video can be found in the Science paper “Total synthesis of himastatin” by D’Angelo et al.

Related to images 6848 and 6850.

A 20-µm thick section of mouse midbrain. The nerve cells are transparent and weren’t stained. Instead, the color is generated by interaction of white polarized light with the molecules in the cells and indicates their orientation.

The image was obtained with a polychromatic polarizing microscope that shows the polychromatic birefringent image with hue corresponding to the slow axis orientation. More information about the microscopy that produced this image can be found in the Scientific Reports paper “Polychromatic Polarization Microscope: Bringing Colors to a Colorless World” by Shribak.

Composite image of beta-galactosidase showing how cryo-EM’s resolution has improved dramatically in recent years. Older images to the left, more recent to the right. Related to image 5882. NIH Director Francis Collins featured this on his blog on January 14, 2016.

E. coli bacteria normally live harmlessly in our intestines, but some cause disease by making toxins. One of these toxins, called Shiga toxin (green), inactivates host ribosomes (purple) by mimicking their normal binding partners, the EF-Tu elongation factor (red) complexed with Phe-tRNAPhe (orange).

Find these in the RCSB Protein Data Bank: Shiga toxin 2 (PDB entry 7U6V) and Phe-tRNA (PDB entry 1TTT).

More information about this work can be found in the J. Biol. Chem. paper "Cryo-EM structure of Shiga toxin 2 in complex with the native ribosomal P-stalk reveals residues involved in the binding interaction" by Kulczyk et. al.

An atomic force microscopy image shows DNA folded into an intricate, computer-designed structure. Image is featured on Biomedical Beat blog post Cool Image: DNA Origami. See also related image 3689 .

In this video, Rice University scientists used molecular modeling with a mathematical algorithm called AWSEM (for associative memory, water-mediated, structure and energy model) and structural data to analyze how a transcription factor called nuclear factor kappa B (NFkB) is removed from DNA to stop gene activation. AWSEM uses the interacting energies of their components to predict how proteins fold. At the start, the NFkB dimer (green and yellow, in the center) grips DNA (red, to the left), which activates the transcription of genes. IkB (blue, to the right), an inhibitor protein, stops transcription when it binds to NFkB and forces the dimer to twist and release its hold on DNA. The yellow domain at the bottom of IkB is the PEST domain, which binds first to NFkB. For more details about this mechanism called molecular stripping, see here.

A crystal of RNase A protein created for X-ray crystallography, which can reveal detailed, three-dimensional protein structures.

Solution NMR structure of protein target WR41 (left) from C. elegans. Noting the unanticipated structural similarity to the ubiquitin protein (Ub) found in all eukaryotic cells, researchers discovered that WR41 is a Ub-like modifier, ubiquitin-fold modifier 1 (Ufm1), on a newly uncovered ubiquitin-like pathway. Subsequently, the PSI group also determined the three-dimensional structure of protein target HR41 (right) from humans, the E2 ligase for Ufm1, using both NMR and X-ray crystallography.

Model of aspartoacylase, a human enzyme involved in brain metabolism.