Cytoplasmic linker protein (CLIP)-170 is a microtubule plus-end-tracking protein that regulates microtubule dynamics and links microtubule ends to different intracellular structures. In this movie, the gene for CLIP-170 has been fused with green fluorescent protein (GFP). When the protein is expressed in cells, the activities can be monitored in real time. Here, you can see CLIP-170 streaming towards the edges of the cell.

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.

Endocytosis is the process by which cells are able to take up membrane and extracellular materials through the formation of a small intracellular bubble, called a vesicle. This process, called membrane budding, is generally by a coating of proteins. This protein coat helps both to deform the membrane and to concentrate specific proteins inside the newly forming vesicle. Clathrin is a coat protein that functions in receptor-mediated endocytosis events at the plasma membrane. This animation shows the process of clathrin-mediated endocytosis. An iron-transport protein called transferrin (blue) is bound to its receptor (purple) on the exterior cell membrane.  Inside the cell, a clathrin cage (shown in white/beige) assembles through interactions with membrane-bound adaptor proteins (green), causing the cell membrane to begin bending. The adaptor proteins also bind to receptors for transferrin, capturing them in the growing vesicle. Molecules of a protein called dynamin (purple) are then recruited to the neck of the vesicle and are involved in separating the membranes of the cell and the vesicle. Soon after the vesicle has budded off the membrane, the clathrin cage is disassembled. This disassembly is mediated by another protein called HSC70 (yellow), and its cofactor protein auxilin (orange).

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

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.

X-ray co-crystal structure of Src kinase bound to a DNA-templated macrocycle inhibitor. Related to 3413, 3415, 3416, 3417, 3418, and 3419.

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.

Like a watch wrapped around a wrist, a special enzyme encircles the double helix to repair a broken strand of DNA. Without molecules that can mend such breaks, cells can malfunction, die, or become cancerous. Related to image 2330.

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.

The HIV capsid is a pear-shaped structure that is made of proteins the virus needs to mature and become infective. The capsid is inside the virus and delivers the virus' genetic information into a human cell. To better understand how the HIV capsid does this feat, scientists have used computer programs to simulate its assembly. This image shows a series of snapshots of the steps that grow the HIV capsid. A model of a complete capsid is shown on the far right of the image for comparison; the green, blue and red colors indicate different configurations of the capsid protein that make up the capsid “shell.” The bar in the left corner represents a length of 20 nanometers, which is less than a tenth the size of the smallest bacterium. Computer models like this also may be used to reconstruct the assembly of the capsids of other important viruses, such as Ebola or the Zika virus. The studies reporting this research were published in Nature Communications and Nature. To learn more about how researchers used computer simulations to track the assembly of the HIV capsid, see this press release from the University of Chicago.

Network diagram showing a map of protein-protein interactions in a yeast (Saccharomyces cerevisiae) cell. This cluster includes 78 percent of the proteins in the yeast proteome. The color of a node represents the phenotypic effect of removing the corresponding protein (red, lethal; green, nonlethal; orange, slow growth; yellow, unknown).

Protein kinases—enzymes that add phosphate groups to molecules—are cancer chemotherapy targets because they play significant roles in almost all aspects of cell function, are tightly regulated, and contribute to the development of cancer and other diseases if any alterations to their regulation occur. Genetic abnormalities affecting the c-Abl tyrosine kinase are linked to chronic myelogenous leukemia, a cancer of immature cells in the bone marrow. In the noncancerous form of the protein, binding of a myristoyl group to the kinase domain inhibits the activity of the protein until it is needed (top left shows the inactive form, top right shows the open and active form). The cancerous variant of the protein, called Bcr-Abl, lacks this autoinhibitory myristoyl group and is continually active (bottom). ATP is shown in green bound in the active site of the kinase.

Find these in the RCSB Protein Data Bank: c-Abl tyrosine kinase and regulatory domains (PDB entry 1OPL) and F-actin binding domain (PDB entry 1ZZP).

The chemical structure of the morphine molecule

This eerily glowing blob isn't an alien or a creature from the deep sea--it's a mouse embryo just eight and a half days old. The green shell and core show a protein called Smad4. In the center, Smad4 is telling certain cells to begin forming the mouse's liver and pancreas. Researchers identified a trio of signaling pathways that help switch on Smad4-making genes, starting immature cells on the path to becoming organs. The research could help biologists learn how to grow human liver and pancreas tissue for research, drug testing and regenerative medicine. In addition to NIGMS, NIH's National Institute of Diabetes and Digestive and Kidney Diseases also supported this work.

This illustration represents the early life of a protein—specifically, apomyoglobin—as it is synthesized by a ribosome and emerges from the ribosomal tunnel, which contains the newly formed protein's conformation. The synthesis occurs in the complex swirl of the cell medium, filled with interactions among many molecules. Researchers in Silvia Cavagnero's laboratory are studying the structure and dynamics of newly made proteins and polypeptides using spectroscopic and biochemical techniques.

High-resolution time lapse of epithelial (skin) cell migration and wound healing. It shows an image taken every 13 seconds over the course of almost 14 minutes. The images were captured with quantitative orientation-independent differential interference contrast (DIC) microscope (left) and a conventional DIC microscope (right).

More information about the research that produced this video can be found in the Journal of Microscopy paper “An Orientation-Independent DIC Microscope Allows High Resolution Imaging of Epithelial Cell Migration and Wound Healing in a Cnidarian Model” by Malamy and Shribak.

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.

This fruit fly spermatid recycles various molecules, including malformed or damaged proteins. Actin filaments (red) in the cell draw unwanted proteins toward a barrel-shaped structure called the proteasome (green clusters), which degrades the molecules into their basic parts for re-use.

Histone proteins loop together with double-stranded DNA to form a structure that resembles beads on a string. See image 2561 for a labeled version of this illustration. Featured in The New Genetics.

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 2572.

This image is featured on the poster for Dr. Rommie Amaro's 2017 Stetten Lecture. It depicts a detailed physical model of an influenza virus, incorporating information from several structural data sources. The small molecules around the virus are sialic acid molecules. The virus binds to and cleaves sialic acid as it enters and exits host cells. Researchers are building these highly detailed molecular scale models of different biomedical systems and then “bringing them to life” with physics-based methods, either molecular or Brownian dynamics simulations, to understand the structural dynamics of the systems and their complex interactions with drug or substrate molecules.

Scientists use nuclear magnetic spectroscopy (NMR) to determine the detailed, 3D structures of molecules.

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.

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

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.

Cdc42, a member of the Rho family of small guanosine triphosphatase (GTPase) proteins, regulates multiple cell functions, including motility, proliferation, apoptosis, and cell morphology. In order to fulfill these diverse roles, the timing and location of Cdc42 activation must be tightly controlled. Klaus Hahn and his research group use special dyes designed to report protein conformational changes and interactions, here in living neutrophil cells. Warmer colors in this image indicate higher levels of activation. Cdc42 looks to be activated at cell protrusions.

Related to images 2451, 2452, and 2453.

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.

Crystals of porcine alpha amylase protein created for X-ray crystallography, which can reveal detailed, three-dimensional protein structures.

Model of an enzyme, dUTP pyrophosphatase, from Mycobacterium tuberculosis. Drugs targeted to this enzyme might inhibit the replication of the bacterium that causes most cases of tuberculosis.

The receptor is shown bound to an antagonist, ML056.

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. Related to video 3307 that shows the structure from different angles. From a Brookhaven National Laboratory news release, "Study Reveals How Protein Machinery Binds and Wraps DNA to Start Replication."

Structure of the bacterial antitoxin protein GhoS. GhoS inhibits the production of a bacterial toxin, GhoT, which can contribute to antibiotic resistance. GhoS is the first known bacterial antitoxin that works by cleaving the messenger RNA that carries the instructions for making the toxin. More information can be found in the paper: Wang X, Lord DM, Cheng HY, Osbourne DO, Hong SH, Sanchez-Torres V, Quiroga C, Zheng K, Herrmann T, Peti W, Benedik MJ, Page R, Wood TK. A new type V toxin-antitoxin system where mRNA for toxin GhoT is cleaved by antitoxin GhoS. Nat Chem Biol. 2012 Oct;8(10):855-61. Related to 3427.

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.

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 CCD-1 molecule and a molecule of the antibiotic cefotaxime bound together. The structure revealed that CCD-1 provides extensive hydrogen bonding and stabilization of the antibiotic in the active site, leading to efficient degradation of the antibiotic.

Related to images 6764, 6765, and 6767.

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.

Crystal structure of the beta2-adrenergic receptor protein. This is the first known structure of a human G protein-coupled receptor, a large family of proteins that control critical bodily functions and the action of about half of today's pharmaceuticals. Featured as one of the November 2007 Protein Structure Initiative Structures of the Month.

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

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

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).

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 2513 and 2514 for other versions of this illustration. Featured in The Structures of Life.

An NMR solution structure model of the transfer RNA splicing enzyme endonuclease in humans (subunit Sen15). This represents the first structure of a eukaryotic tRNA splicing endonuclease subunit.

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

The receptor is shown bound to an inverse agonist, ZM241385.

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.

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.

A growing Vibrio cholerae (cholera) biofilm. Cholera bacteria form colonies called biofilms that enable them to resist antibiotic therapy within the body and other challenges to their growth.

Each slightly curved comma shape represents an individual bacterium from assembled confocal microscopy images. Different colors show each bacterium’s position in the biofilm in relation to the surface on which the film is growing.

This image shows how the CRISPR surveillance complex is disabled by two copies of anti-CRISPR protein AcrF1 (red) and one AcrF2 (light green). These anti-CRISPRs block access to the CRISPR RNA (green tube) preventing the surveillance complex from scanning and targeting invading viral DNA for destruction.

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.