This network map shows molecular interactions (yellow) associated with a congenital condition that causes heart arrhythmias and the targets for drugs that alter these interactions (red and blue).

Force vectors computed from actin cytoskeleton flow. This is an example of NIH-supported research on single-cell analysis. Related to 2798, 2800, 2801, 2802 and 2803.

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.

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

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.

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 2494, 2495, and 2488.

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."

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).

The atomic structure of the morphine biosynthetic enzyme salutaridine reductase bound to the cofactor NADPH. The substrate salutaridine is shown entering the active site.

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, 2495, and 2488.

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.

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 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 2537 for other versions of this image. Featured in Medicines By Design.

A three-dimensional representation of the structure of E2, a key antigen protein involved with hepatitis C virus infection.

Opioid receptors on the surfaces of brain cells are involved in pleasure, pain, addiction, depression, psychosis, and other conditions. The receptors bind to both innate opioids and drugs ranging from hospital anesthetics to opium. Researchers at The Scripps Research Institute, supported by the NIGMS Protein Structure Initiative, determined the first three-dimensional structure of a human opioid receptor, a kappa-opioid receptor. In this illustration, the submicroscopic receptor structure is shown while bound to an agonist (or activator). The structure is superimposed on a poppy flower, the source of opium.

The illustration shows the capsid of human immunodeficiency virus (HIV) whose molecular features were resolved with cryo-electron microscopy (cryo-EM). On the left, the HIV capsid is "naked," a state in which it would be easily detected by and removed from cells. However, as shown on the right, when the viral capsid binds to and is covered with a host protein, called cyclophilin A (shown in red), it evades detection and enters and invades the human cell to use it to establish an infection. To learn more about how cyclophilin A helps HIV infect cells and how scientists used cryo-EM to find out the mechanism by which the HIV capsid attaches to cyclophilin A, see this news release by the University of Illinois. A study reporting these findings was published in the journal Nature Communications.

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

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.

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.

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 2454.

Histone proteins loop together with double-stranded DNA to form a structure that resembles beads on a string. See image 2560 for an unlabeled version of this illustration. Featured in The New Genetics.

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 illustration shows a protein substrate (red) that is bound through its ubiquitin chain (blue) to one of the ubiquitin receptors of the proteasome (Rpn10, yellow). The substrate's flexible engagement region 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 small 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 video 3764.

Enzymes convert substrates into products very quickly. See image 2522 for a labeled version of this illustration. Featured in The Chemistry of Health.

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.

Active site of E. coli response regulator PhoB.

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.

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.

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.

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

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 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.

This is a magnified view of an Arabidopsis thaliana leaf after several days of infection with the pathogen Hyaloperonospora arabidopsidis. The pathogen's blue hyphae grow throughout the leaf. On the leaf's edges, stalk-like structures called sporangiophores are beginning to mature and will release the pathogen's spores. Inside the leaf, the large, deep blue spots are structures called oopsorangia, also full of spores. Compare this response to that shown in Image 2781. Jeff Dangl has been funded by NIGMS to study the interactions between pathogens and hosts that allow or suppress infection.

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.

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

This image shows a computer-generated, three-dimensional map of the rotavirus structure. This virus infects humans and other animals and causes severe diarrhea in infants and young children. By the age of five, almost every child in the world has been infected with this virus at least once. Scientists have found a vaccine against rotavirus, so in the United States there are very few fatalities, but in developing countries and in places where the vaccine is unavailable, this virus is responsible for more than 200,000 deaths each year.

The rotavirus comprises three layers: the outer, middle and inner layers. On infection, the outer layer is removed, leaving behind a "double-layered particle." Researchers have studied the structure of this double-layered particle with a transmission electron microscope. Many images of the virus at a magnification of ~50,000x were acquired, and computational analysis was used to combine the individual particle images into a three-dimensional reconstruction.

The image was rendered by Melody Campbell (PhD student at TSRI). Work that led to the 3D map was published in Campbell et al. Movies of ice-embedded particles enhance resolution in electron cryo-microscopy. Structure. 2012;20(11):1823-8. PMCID: PMC3510009.

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

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 3428.

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.

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.

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.

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.

RNA polymerase (purple) is a complex enzyme at the heart of transcription. During this process, the enzyme unwinds the DNA double helix and uses one strand (darker orange) as a template to create the single-stranded messenger RNA (green), later used by ribosomes for protein synthesis.

From the RNA polymerase II elongation complex of Saccharomyces cerevisiae (PDB entry 1I6H) as seen in PDB-101's What is a Protein? video.

X-ray structure of a DNA repair enzyme superfamily representative from the human gastrointestinal bacterium Enterococcus faecalis. European scientists used this structure to generate homologous structures. Featured as the May 2007 Protein Structure Initiative Structure of the Month.

Serum albumin (SA) is the most abundant protein in the blood plasma of mammals. SA has a characteristic heart-shape structure and is a highly versatile protein. It helps maintain normal water levels in our tissues and carries almost half of all calcium ions in human blood. SA also transports some hormones, nutrients and metals throughout the bloodstream. Despite being very similar to our own SA, those from other animals can cause some mild allergies in people. Therefore, some scientists study SAs from humans and other mammals to learn more about what subtle structural or other differences cause immune responses in the body.

Related to entries 3744 and 3746

Model of the enzyme nicotinic acid phosphoribosyltransferase. This enzyme, from the archaebacterium, Pyrococcus furiosus, is expected to be structurally similar to a clinically important human protein called B-cell colony enhancing factor based on amino acid sequence similarities and structure prediction methods. The structure consists of identical protein subunits, each shown in a different color, arranged in a ring.

Kinases are enzymes that add phosphate groups (red-yellow structures) to proteins (green), assigning the proteins a code. In this reaction, an intermediate molecule called ATP (adenosine triphosphate) donates a phosphate group from itself, becoming ADP (adenosine diphosphate). See image 2534 for an unlabeled version of this illustration. Featured in Medicines By Design.

An RNA molecule dynamically refolds itself as it is being synthesized. When the RNA is short, it ties itself into a “knot” (dark purple). For this domain to slip its knot, about 5 seconds into the video, another newly forming region (fuchsia) wiggles down to gain a “toehold.” About 9 seconds in, the temporarily knotted domain untangles and unwinds. Finally, at about 23 seconds, the strand starts to be reconfigured into the shape it needs to do its job in the cell.

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.

In SARS-CoV-2, the virus that causes COVID-19, nucleocapsid is a complex molecule with many functional parts. One section folds into an RNA-binding domain, with a groove that grips a short segment of the viral genomic RNA. Another section folds into a dimerization domain that brings two nucleocapsid molecules together. The rest of the protein is intrinsically disordered, forming tails at each end of the protein chain and a flexible linker that connects the two structured domains. These disordered regions assist with RNA binding and orchestrate association of nucleocapsid dimers into larger assemblies that package the RNA in the small space inside virions. Nucleocapsid is in magenta and purple, and short RNA strands are in yellow.

Find these in the RCSB Protein Data Bank: RNA-binding domain (PDB entry 7ACT) and Dimerization domain (PDB entry 6WJI).