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

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

Shiga toxin (green) is sorted from the endosome into membrane tubules (red), which then pinch off and move to the Golgi apparatus.

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.

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.

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.

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.

Gene transcription is a process by which information encoded in DNA is transcribed into RNA. It's essential for all life and requires the activity of proteins, called transcription factors, that detect where in a DNA strand transcription should start. In eukaryotes (i.e., those that have a nucleus and mitochondria), a protein complex comprising 14 different proteins is responsible for sniffing out transcription start sites and starting the process. This complex represents the core machinery to which an enzyme, named RNA polymerase, can bind to and read the DNA and transcribe it to RNA. Scientists have used cryo-electron microscopy (cryo-EM) to visualize the TFIID-RNA polymerase-DNA complex in unprecedented detail. This animation shows the different TFIID components as they contact DNA and recruit the RNA polymerase for gene transcription.

To learn more about the research that has shed new light on gene transcription, see this news release from Berkeley Lab.

Related to image 3766.

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.

Three views of the entire nuclear lamina of a HeLa cell produced by tilted light sheet 3D single-molecule super-resolution imaging using a platform termed TILT3D.
See 6572 for a 3D view of this structure.

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

Cell showing overproduction of the ARTS protein (red). ARTS triggers apoptosis, as shown by the activation of caspase-3 (green) a key tool in the cell's destruction. The nucleus is shown in blue. Image is featured in October 2015 Biomedical Beat blog post Cool Images: A Halloween-Inspired Cell Collection.

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.

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.

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.

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 porcine alpha amylase protein created for 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 2453.

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

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 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.

A computer-generated sketch of a DNA origami folded into a flower-and-bird structure. See also related image 3690.

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.

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.

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).

CellPack image of the H1N1 influenza virus, with hemagglutinin and neuraminidase glycoproteins in green and red, respectively, on the outer envelope (white); matrix protein in gray, and ribonucleoprotein particles inside the virus in red and green. Related to image 6356.

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.

Model of an enzyme, PanB, from Mycobacterium tuberculosis, the bacterium that causes most cases of tuberculosis. This enzyme is an attractive drug target.

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.

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

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

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.

Salk researchers captured the structure of a protein complex called an intasome (center) that lets viruses similar to HIV establish permanent infection in their hosts. The intasome hijacks host genomic material, DNA (white) and histones (beige), and irreversibly inserts viral DNA (blue). The image was created by Jamie Simon and Dmitry Lyumkis. Work that led to the 3D map was published in: Ballandras-Colas A, Brown M, Cook NJ, Dewdney TG, Demeler B, Cherepanov P, Lyumkis D, & Engelman AN. (2016). Cryo-EM reveals a novel octameric integrase structure for ?-retroviral intasome function. Nature, 530(7590), 358—361

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.

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.

This is a fibroblast, a connective tissue cell that plays an important role in wound healing. Normal fibroblasts have smooth edges. In contrast, this spiky cell is missing a protein that is necessary for proper construction of the cell's skeleton. Its jagged shape makes it impossible for the cell to move normally. In addition to compromising wound healing, abnormal cell movement can lead to birth defects, faulty immune function, and other health problems.

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

X-ray co-crystal structure of Src kinase bound to a DNA-templated macrocycle inhibitor. Related to images 3413, 3414, 3415, 3416, 3417, and 3418.

Cilia (cilium in singular) are complex molecular machines found on many of our cells. One component of cilia is the doublet microtubule, a major part of cilia’s skeletons that give them support and shape. This animated video illustrates the structure of doublet microtubules, which contain 451 protein chains that were mapped using cryo-electron microscopy. Image can be found here 6548.

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.

Dengue virus is a mosquito-borne illness that infects millions of people in the tropics and subtropics each year. Like many viruses, dengue is enclosed by a protective membrane. The proteins that span this membrane play an important role in the life cycle of the virus. Scientists used cryo-EM to determine the structure of a dengue virus at a 3.5-angstrom resolution to reveal how the membrane proteins undergo major structural changes as the virus matures and infects a host. The image shows a side view of the structure of a protein composed of two smaller proteins, called E and M. Each E and M contributes two molecules to the overall protein structure (called a heterotetramer), which is important for assembling and holding together the viral membrane, i.e., the shell that surrounds the genetic material of the dengue virus. The dengue protein's structure has revealed some portions in the protein that might be good targets for developing medications that could be used to combat dengue virus infections. For more on cryo-EM see the blog post Cryo-Electron Microscopy Reveals Molecules in Ever Greater Detail. You can watch a rotating view of the dengue virus surface structure in video 3748.

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

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

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

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

Scientists recently discovered the full molecular structure of telomerase, an enzyme important to aging and cancer. Within each cell, telomerase maintains the telomeres, or end pieces, of a chromosome, preserving genetic data and extending the life of the cell. In their study, a team from UCLA and UC Berkeley found the subunit p50, shown in red, to be a keystone in the enzyme's structure and function. Featured in the May 16, 2013 issue of Biomedical Beat.

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.

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

NMR solution structure of a plant protein that may function in host defense. This protein was expressed in a convenient and efficient wheat germ cell-free system. Featured as the June 2007 Protein Structure Initiative Structure of the Month.

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.

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.