A mouse liver glows after being tagged with specially designed infrared-fluorescent protein (IFP). Since its discovery in 1962, green fluorescent protein (GFP) has become an invaluable resource in biomedical imaging. But because of its short wavelength, the light that makes GFP glow doesn't penetrate far in whole animals. So University of California, San Diego cell biologist Roger Tsien--who shared the 2008 Nobel Prize in chemistry for groundbreaking work with GFP--made infrared-fluorescent proteins (IFPs) that shine under longer-wavelength light, allowing whole-body imaging in small animals.

To develop a system for studying cell motility in unnatrual conditions -- a microscope slide instead of the body -- Tom Roberts and Katsuya Shimabukuro at Florida State University disassembled and reconstituted the motility parts used by worm sperm cells.

RNA incorporated into the CRISPR surveillance complex is positioned to scan across foreign DNA. Cryo-EM density from a 3Å reconstruction is shown as a yellow mesh.

Three-dimensional reconstruction of a tubular matrix in a thin section of the peripheral endoplasmic reticulum between the plasma membranes of the cell.
The endoplasmic reticulum (ER) is a continuous membrane that extends like a net from the envelope of the nucleus outward to the cell membrane. The ER plays several roles within the cell, such as in protein and lipid synthesis and transport of materials between organelles.
Shown here are super-resolution microscopic images of the peripheral ER showing the structure of an ER tubular matrix between the plasma membranes of the cell. See image 5857 for a more detailed view of the area outlined in white in this image. For another view of the ER tubular matrix see image 5855

A crystal of bovine milk alpha-lactalbumin protein created for X-ray crystallography, which can reveal detailed, three-dimensional protein structures.

Disassembly of vasculature in kdr:GFP frogs following addition of 250 µM TBZ. Related to images 3404 and 3505.

Zika virus is shown in cross section at center left. On the outside, it includes envelope protein (red) and membrane protein (magenta) embedded in a lipid membrane (light purple). Inside, the RNA genome (yellow) is associated with capsid proteins (orange). The viruses are shown interacting with receptors on the cell surface (green) and are surrounded by blood plasma molecules at the top.

Dynein (green) is a motor protein that “walks” along microtubules (red, part of the cytoskeleton) and carries its cargo along with it. This video was captured through fluorescence microscopy.

This sculpture made of purple and clear glass beads depicts bacteriophage Phi174, a virus that infects bacteria. It rests on a surface that portrays an adaptive landscape, a conceptual visualization. The ridges represent the gene combinations associated with the greatest fitness levels of the virus, as measured by how quickly the virus can reproduce itself. Phi174 is an important model system for studies of viral evolution because its genome can readily be sequenced as it evolves under defined laboratory conditions.

The feeding tube, or pharynx, of a planarian worm with cilia shown in red and muscle fibers shown in green

A knotted protein from an archaebacterium called Methanobacterium thermoautotrophicam. This organism breaks down waste products and produces methane gas. Protein folding theory previously held that forming a knot was beyond the ability of a protein, but this structure, determined at Argonne's Structural Biology Center, proves differently. Researchers theorize that this knot stabilizes the amino acid subunits of the protein.

Like a strand of white pearls, DNA wraps around an assembly of special proteins called histones (colored) to form the nucleosome, a structure responsible for regulating genes and condensing DNA strands to fit into the cell's nucleus. Researchers once thought that nucleosomes regulated gene activity through their histone tails (dotted lines), but a 2010 study revealed that the structures' core also plays a role. The finding sheds light on how gene expression is regulated and how abnormal gene regulation can lead to cancer.

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

The enzyme CCP is found in the mitochondria of baker’s yeast. Scientists study the chemical reactions that CCP triggers, which involve a water molecule, iron, and oxygen. This structure was determined using an X-ray free electron laser.

Featured in the March 15, 2012 issue of Biomedical Beat. Related to Hsp33 Figure 1, image 3354.

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 images 2491, 2494, and 2488.

X-ray co-crystal structure of Src kinase bound to a DNA-templated macrocycle inhibitor. Related to 3414, 3415, 3416, 3417, 3418, and 3419.

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.

The lubber grasshopper, found throughout the southern United States, is frequently used in biology classes to teach students about the respiratory system of insects. Unlike mammals, which have red blood cells that carry oxygen throughout the body, insects have breathing tubes that carry air through their exoskeleton directly to where it's needed. This image shows the breathing tubes embedded in the weblike sheath cells that cover developing egg chambers.

This image was part of the Life: Magnified exhibit that ran from June 3, 2014, to January 21, 2015, at Dulles International Airport.

This image represents the structure of TrpRS, a novel member of the tryptophanyl tRNA-synthetase family of enzymes. By helping to link the amino acid tryptophan to a tRNA molecule, TrpRS primes the amino acid for use in protein synthesis. A cluster of iron and sulfur atoms (orange and red spheres) was unexpectedly found in the anti-codon domain, a key part of the molecule, and appears to be critical for the function of the enzyme. TrpRS was discovered in Thermotoga maritima, a rod-shaped bacterium that flourishes in high temperatures.

When the heat shock protein hsp33 is folded, it is inactive and contains a zinc ion, stabilizing the redox sensitive domain (orange). In the presence of an environmental stressor, the protein releases the zinc ion, which leads to the unfolding of the redox domain. This unfolding causes the chaperone to activate by reaching out its "arm" (green) to protect other proteins.

This short video shows a model of the DNA helicase in yeast. This DNA helicase has 11 proteins that work together to unwind DNA during the process of copying it, called DNA replication. Scientists used a technique called cryo-electron microscopy (cryo-EM), which allowed them to study the helicase structure in solution rather than in static crystals. Cryo-EM in combination with computer modeling therefore allows researchers to see movements and other dynamic changes in the protein. The cryo-EM approach revealed the helicase structure at much greater resolution than could be obtained before. The researchers think that a repeated motion within the protein as shown in the video helps it move along the DNA strand. To read more about DNA helicase and this proposed mechanism, see this news release by Brookhaven National Laboratory.

Structure of a magnesium transporter protein from an antibiotic-resistant bacterium (Enterococcus faecalis) found in the human gut. Featured as one of the June 2007 Protein Sructure Initiative Structures of the Month.

Proteins are made of amino acids hooked end-to-end like beads on a necklace. To become active, proteins must twist and fold into their final, or "native," conformation. A protein's final shape enables it to accomplish its function. Featured in The Structures of Life.

Superresolution microscopy work on endoplasmic reticulum (ER) in the peripheral areas of the cell showing details of the structure and arrangement in a complex web of tubes.
The ER is a continuous membrane that extends like a net from the envelope of the nucleus outward to the cell membrane. The ER plays several roles within the cell, such as in protein and lipid synthesis and transport of materials between organelles. The ER has a flexible structure to allow it to accomplish these tasks by changing shape as conditions in the cell change. Shown here an image created by super-resolution microscopy of the ER in the peripheral areas of the cell showing details of the structure and the arrangements in a complex web of tubes. Related to images 5856 and 5857.

The G switch allows our bodies to respond rapidly to hormones. See images 2537 and 2538 for labeled versions of this image. Featured in Medicines By Design.

Model of a major secreted protein of unknown function, which is only found in mycobacteria, the class of bacteria that causes tuberculosis. Based on structural similarity, this protein may be involved in host-bacterial interactions.

Coronaviruses are enveloped viruses responsible for 30 percent of mild respiratory infections and atypical deadly pneumonia in humans worldwide. These deadly pneumonia include those caused by infections with severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). The coronavirus spike glycoprotein mediates virus entry into cells and represents an important therapeutic target. The illustration shows a viral membrane decorated with spike glycoproteins; highlighted in red is a potential neutralization site, which is a protein sequence that might be used as a target for vaccines to combat viruses such as MERS-CoV and other coronaviruses.

This is the first structure of a protein derived from the metagenomic sequences collected during the Sorcerer II Global Ocean Sampling project. The crystal structure shows a barrel protein with a ferredoxin-like fold and a long chain fatty acid in a deep cleft (shaded red). Featured as one of the August 2007 Protein Structure Initiative Structures of the Month.

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.

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.

The TRPA1 protein is responsible for the burn you feel when you taste a bite of sushi topped with wasabi. Known therefore informally as the "wasabi receptor," this protein forms pores in the membranes of nerve cells that sense tastes or odors. Pungent chemicals like wasabi or mustard oil cause the pores to open, which then triggers a tingling or burn on our tongue. This receptor also produces feelings of pain in response to chemicals produced within our own bodies when our tissues are damaged or inflamed. Researchers used cryo-EM to reveal the structure of the wasabi receptor at a resolution of about 4 angstroms (a credit card is about 8 million angstroms thick). This detailed structure can help scientists understand both how we feel pain and how we can limit it by developing therapies to block the receptor. For more on cryo-EM see the blog post Cryo-Electron Microscopy Reveals Molecules in Ever Greater Detail.

CCD-1 is an enzyme produced by the bacterium Clostridioides difficile that helps it resist antibiotics. Using X-ray crystallography, researchers determined the structure of a complex between CCD-1 and the antibiotic cefotaxime (purple, yellow, and blue molecule). The structure revealed that CCD-1 provides extensive hydrogen bonding (shown as dotted lines) and stabilization of the antibiotic in the active site, leading to efficient degradation of the antibiotic.

Related to images 6764, 6765, and 6766.

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.

From PDB entry 3c6k, Crystal structure of human spermine synthase in complex with spermidine and 5-methylthioadenosine.

Model of the enzyme aminopeptidase N from the human pathogen Neisseria meningitidis, which can cause meningitis epidemics. The structure provides insight on the active site of this important molecule.

The molecule on the left is an electrostatic potential map of the van der Waals surface of the transition state for human purine nucleoside phosphorylase. The colors indicate the electron density at any position of the molecule. Red indicates electron-rich regions with negative charge and blue indicates electron-poor regions with positive charge. The molecule on the right is called DADMe-ImmH. It is a chemically stable analogue of the transition state on the left. It binds to the enzyme millions of times tighter than the substrate. This inhibitor is in human clinical trials for treating patients with gout. This image appears in Figure 4, Schramm, V.L. (2011) Annu. Rev. Biochem. 80:703-732.

This illustration highlights spherical pre-synaptic vesicles that carry the neurotransmitter glutamate. The presynaptic and postsynaptic membranes are shown with proteins relevant for transmitting and modulating the neuronal signal.

PDB 101’s Opioids and Pain Signaling video explains how glutamatergic synapses are involved in the process of pain signaling.

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 2570 and 2571.

A protein called kinesin (blue) is in charge of moving cargo around inside cells and helping them divide. It's powered by biological fuel called ATP (bright yellow) as it scoots along tube-like cellular tracks called microtubules (gray).

The receptor is shown bound to an antagonist, JDTic.

A cross section of the measles virus in which six proteins work together to infect cells. The measles virus is extremely infectious; 9 out of 10 people exposed will contract the disease. Fortunately, an effective vaccine protects against infection.

For a zoomed-in look at the six important proteins, see Measles Virus Proteins.

A segment of siRNA, shown in red, guides a "slicer" protein called Argonaute (multi-colored twists and corkscrews) to the target RNA molecules.

Crystals of fungal lipase protein created for X-ray crystallography, which can reveal detailed, three-dimensional protein structures.

On top, the brain of a sleep-deprived fly glows orange because of Bruchpilot, a communication protein between brain cells. These bright orange brain areas are associated with learning. On the bottom, a well-rested fly shows lower levels of Bruchpilot, which might make the fly ready to learn after a good night's rest.

The goal of the Protein Structure Initiative (PSI) is to determine the three-dimensional shapes of a wide range of proteins by solving the structures of representative members of each protein family found in nature. The collection of structures should serve as a valuable resource for biomedical research scientists.

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 3D reconstruction, created using cryo-electron microscopy, of an ion channel known as the full-length serotonin receptor in complex with the antinausea drug granisetron (orange). Ion channels are proteins in cell membranes that help regulate many processes.

Detail of a subunit of the capsid, or outer cover, of bacteriophage P22, a virus that infects the Salmonella bacteria. Cryo-electron microscopy (cryo-EM) was used to capture details of the capsid proteins, each shown here in a separate color. Thousands of cryo-EM scans capture the structure and shape of all the individual proteins in the capsid and their position relative to other proteins. A computer model combines these scans into the image shown here. Related to image 5874.

This image shows a normal fibroblast, a type of cell that is common in connective tissue and frequently studied in research labs. This cell has a healthy skeleton composed of actin (red) and microtubles (green). Actin fibers act like muscles to create tension and microtubules act like bones to withstand compression.

This image was part of the Life: Magnified exhibit that ran from June 3, 2014, to January 21, 2015, at Dulles International Airport.