Model of a protein involved in cell division from Mycoplasma pneumoniae. This model, based on X-ray crystallography, revealed a structural domain not seen before. The protein is thought to be involved in cell division and cell wall biosynthesis.

Model of the mandelate racemase enzyme from Bacillus subtilis, a bacterium commonly found in soil.

The G switch allows our bodies to respond rapidly to hormones. G proteins act like relay batons to pass messages from circulating hormones into cells. A hormone (red) encounters a receptor (blue) in the membrane of a cell. Next, a G protein (green) becomes activated and makes contact with the receptor to which the hormone is attached. Finally, the G protein passes the hormone's message to the cell by switching on a cell enzyme (purple) that triggers a response. See image 2536 and 2538 for other versions of this image. Featured in Medicines By Design.

The molecules that glow blue in these cultured cells prevent the expression of the mutant proteins that cause Huntington's disease. Biochemist David Corey and others at UT Southwestern Medical Center designed the molecules to specifically target the genetic repeats that code for harmful proteins in people with Huntington's disese. People with Huntington's disease and similar neurodegenerative disorders often have extra copies of a gene segment. Moving from cell cultures to animals will help researchers further explore the potential of their specially crafted molecule to treat brain disorders. In addition to NIGMS, NIH's National Institute of Neurological Disorders and Stroke and National Institute of Biomedical Imaging and Bioengineering also funded this work.

This crystal structure shows a conserved hypothetical protein from Mycobacterium tuberculosis. Only 12 other proteins share its sequence homology, and none has a known function. This structure indicates the protein may play a role in metabolic pathways. Featured as one of the August 2007 Protein Structure Initiative Structures of the Month.

3D image of Caulobacter bacterium with various components highlighted: cell membranes (red and blue), protein shell (green), protein factories known as ribosomes (yellow), and storage granules (orange).

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.

Enzymes speed up chemical reactions by reducing the amount of energy needed for the reactions. The substrate (lactose) binds to the active site of the enzyme (lactase) and is converted into products (sugars).

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.

Living primary mouse embryonic fibroblasts. Mitochondria (green) stained with the mitochondrial membrane potential indicator, rhodamine 123. Nuclei (blue) are stained with DAPI. Caption from a November 26, 2012 news release from U Penn (Penn Medicine).

Rhodopsin is a pigment in the rod cells of the retina (back of the eye). It is extremely light-sensitive, supporting vision in low-light conditions. Here, it is attached to arrestin, a protein that sends signals in the body. This structure was determined using an X-ray free electron laser.

Viruses have been the foes of animals and other organisms for time immemorial. For almost as long, they've stayed well hidden from view because they are so tiny (they aren't even cells, so scientists call the individual virus a "particle"). This image shows a molecular model of a particle of the Rous sarcoma virus (RSV), a virus that infects and sometimes causes cancer in chickens. In the background is a photo of red blood cells. The particle shown is "immature" (not yet capable of infecting new cells) because it has just budded from an infected chicken cell and entered the bird's bloodstream. The outer shell of the immature virus is made up of a regular assembly of large proteins (shown in red) that are linked together with short protein molecules called peptides (green).  This outer shell covers and protects the proteins (blue) that form the inner shell of the particle. But as you can see, the protective armor of the immature virus contains gaping holes. As the particle matures, the short peptides are removed and the large proteins rearrange, fusing together into a solid sphere capable of infecting new cells. While still immature, the particle is vulnerable to drugs that block its development. Knowing the structure of the immature particle may help scientists develop better medications against RSV and similar viruses in humans. Scientists used sophisticated computational tools to reconstruct the RSV atomic structure by crunching various data on the RSV proteins to simulate the entire structure of immature RSV.

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.

Proteins are long chains of amino acids. Each protein has a unique amino acid sequence. It is still a mystery how a protein folds into the proper shape based on its sequence. Scientists hope that one day they can "watch" this folding process for any given protein. The dream has been realized, at least partially, through the use of computer simulation.

C. elegans, a tiny roundworm, with a ribosomal protein glowing red and muscle fibers glowing green. Researchers used these worms to study a molecular pathway that affects aging. The ribosomal protein is involved in protein translation and may play a role in dietary restriction-induced longevity. Image created using confocal microscopy.
View group of roundworms here 6582.
View closeup of roundworms here 6583.

X-ray co-crystal structure of Src kinase bound to a DNA-templated macrocycle inhibitor. Related to 3413, 3414, 3416, 3417, 3418, and 3419.

Scientists revealed a detailed image of the genetic defect that causes myotonic dystrophy type 2 and used that information to design drug candidates to counteract the disease.

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

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

Multiple actin filaments (magenta) are organized around a dynamin helical polymer (rainbow colored) in this model derived from cryo-electron tomography. By bundling actin, dynamin increases the strength of a cell’s skeleton and plays a role in cell-cell fusion, a process involved in conception, development, and regeneration.

In plants, as in animals, stem cells can transform into a variety of different cell types. The stem cells at the growing tip of this Arabidopsis plant will soon become flowers. Arabidopsis is frequently studied by cellular and molecular biologists because it grows rapidly (its entire life cycle is only 6 weeks), produces lots of seeds, and has a genome that is easy to manipulate.

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

Trajectories of single molecule labeled cell surface receptors. This is an example of NIH-supported research on single-cell analysis. Related to 2798 , 2799, 2800, 2802 and 2803.

PETase enzyme degrades polyester plastic (polyethylene terephthalate, or PET) into monohydroxyethyl terephthalate (MHET). Then, MHETase enzyme degrades MHET into its constituents ethylene glycol (EG) and terephthalic acid (TPA).

Find these in the RCSB Protein Data Bank: PET hydrolase (PDB entry 5XH3) and MHETase (PDB entry 6QGA).

Gram-negative bacteria perform molecular acrobatics just to eat. Because they're encased by two membranes, they must haul nutrients across both. To test one theory of how the bacteria manage this feat, researchers used computer simulations of two proteins involved in importing vitamin B12. Here, the protein (red) anchored in the inner membrane of bacteria tugs on a much larger protein (green and blue) in the outer membrane. Part of the larger protein unwinds, creating a pore through which the vitamin can pass.

A study published in March 2012 used cryo-electron microscopy to determine the structure of the DNA replication origin recognition complex (ORC), a semi-circular, protein complex (yellow) that recognizes and binds DNA to start the replication process. The ORC appears to wrap around and bend approximately 70 base pairs of double stranded DNA (red and blue). Also shown is the protein Cdc6 (green), which is also involved in the initiation of DNA replication. The video shows the structure from different angles. See related image 3597.

An Arachnoidiscus diatom with a diameter of 190µm. Diatoms are microscopic algae that have cell walls made of silica, which is the strongest known biological material relative to its density. In Arachnoidiscus, the cell wall is a radially symmetric pillbox-like shell composed of overlapping halves that contain intricate and delicate patterns. Sometimes, Arachnoidiscus is called “a wheel of glass.”

This image was taken with the orientation-independent differential interference contrast microscope.

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.

HIV is a retrovirus, a type of virus that carries its genetic material not as DNA but as RNA. Long before anyone had heard of HIV, researchers in labs all over the world studied retroviruses, tracing out their life cycle and identifying the key proteins the viruses use to infect cells. When HIV was identified as a retrovirus, these studies gave AIDS researchers an immediate jump-start. The previously identified viral proteins became initial drug targets. See images 2514 and 2515 for labeled versions of this illustration. Featured in The Structures of Life.

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.

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.

This ribbon drawing of a protein hand drawn and colored by researcher Jane Richardson in 1981 helped originate the ribbon representation of proteins that is now ubiquitous in molecular graphics. The drawing shows the 3-dimensional structure of the protein triose phosphate isomerase. The green arrows represent the barrel of eight beta strands in this structure and the brown spirals show the protein's eight alpha helices. A black and white version of this drawing originally illustrated a review article in Advances in Protein Chemistry, volume 34, titled "Anatomy and Taxonomy of Protein Structures." The illustration was selected as Picture of The Day on the English Wikipedia for November 19, 2009. Other important and beautiful images of protein structures by Jane Richardson are available in her Wikimedia gallery.

The 3D single-molecule super-resolution reconstruction of the entire nuclear lamina in a HeLa cell was acquired using the TILT3D platform. TILT3D combines a tilted light sheet with point-spread function (PSF) engineering to provide a flexible imaging platform for 3D single-molecule super-resolution imaging in mammalian cells.
See 6573 for 3 separate views of this structure.

A zebrafish embryo showing its natural colors. Zebrafish have see-through eggs and embryos, making them ideal research organisms for studying the earliest stages of development. This image was taken in transmitted light under a polychromatic polarizing microscope.

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.

Proteins are 3D structures made up of smaller units. DNA is transcribed to RNA, which in turn is translated into amino acids. Amino acids form a protein strand, which has sections of corkscrew-like coils, called alpha helices, and other sections that fold flat, called beta sheets. The protein then goes through complex folding to produce the 3D structure.

The cryo-EM structure of human adenovirus D26 (HAdV-D26) at near atomic resolution (3.7 Å), determined in collaboration with the NRAMM facility*. In difference to archetype HAdV-C5, the HAdV-D26 is a low seroprevalent viral vector, which is being used to generate Ebola virus vaccines.

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

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

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.

Cryo-electron microscopy (cryo-EM) has the power to capture details of proteins and other small biological structures at the molecular level.  This image shows proteins in the capsid, or outer cover, of bacteriophage P22, a virus that infects the Salmonella bacteria. Each color shows the structure and position of an individual protein in the capsid. 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 three-dimension image shown here. Related to image 5875.

A protein called tubulin (green) accumulates in the center of a nucleus (outlined in pink) from an aging cell. Normally, this protein is kept out of the nucleus with the help of gatekeepers known as nuclear pore complexes. But NIGMS-funded researchers found that wear and tear to long-lived components of the complexes eventually lowers the gatekeepers' guard. As a result, cytoplasmic proteins like tubulin gain entry to the nucleus while proteins normally confined to the nucleus seep out. The work suggests that finding ways to stop the leakage could slow the cellular aging process and possibly lead to new therapies for age-related diseases.

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.

The chemical structure of the morphine molecule

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.

Catalases are some of the most efficient enzymes found in cells. Each catalase molecule can decompose millions of hydrogen peroxide molecules every second—working as an antioxidant to protect cells from the dangerous form of reactive oxygen. Different cells build different types of catalases. The human catalase that protects our red blood cells, shown on the left from PDB entry 1QQW, is composed of four identical subunits and uses a heme/iron group to perform the reaction. Many bacteria scavenge hydrogen peroxide with a larger catalase, shown in the center from PDB entry 1IPH, that uses a similar arrangement of iron and heme. Other bacteria protect themselves with an entirely different catalase that uses manganese ions instead of heme, as shown at the right from PDB entry 1JKU.

The structure of a gene-regulating zinc finger protein bound to DNA.

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.

Ribosomes are complex machines made up of more than 50 proteins and three or four strands of genetic material called ribosomal RNA (rRNA). The busy cellular machines make proteins, which are critical to almost every structure and function in the cell. To do so, they read protein-building instructions, which come as strands of messenger RNA. Ribosomes are found in all forms of cellular life—people, plants, animals, even bacteria. This illustration of a bacterial ribosome was produced using detailed information about the position of every atom in the complex. Several antibiotic medicines work by disrupting bacterial ribosomes but leaving human ribosomes alone. Scientists are carefully comparing human and bacterial ribosomes to spot differences between the two. Structures that are present only in the bacterial version could serve as targets for new antibiotic medications.

Crystals of jack bean concanavalin A protein created for X-ray crystallography, which can reveal detailed, three-dimensional protein structures.

This image is a computer-generated model of the approximately 4.2 million atoms of the HIV capsid, the shell that contains the virus' genetic material. Scientists determined the exact structure of the capsid and the proteins that it's made of using a variety of imaging techniques and analyses. They then entered these data into a supercomputer that produced the atomic-level image of the capsid. This structural information could be used for developing drugs that target the capsid, possibly leading to more effective therapies. Related to image 6601.