Category: Molecular Structures

More Than 25 Years of Competition and Collaboration Advance the Prediction of Protein Shapes


Proteins (such as hemoglobin, actin, and amylase) are workhorse molecules that contribute to virtually every activity in the body. Some of proteins’ many jobs include carrying oxygen from your lungs to the rest of your body (hemoglobin), allowing your muscles to move (actin and myosin), and digesting your food (amylase, pepsin, and lactase). All proteins are made up of chains of amino acids that fold into specific 3D structures, and each protein’s structure allows it to perform its distinct job. Proteins that are misfolded or misshapen can cause diseases such as Parkinson’s or cataracts.

While it’s straightforward to use the genetic code to predict amino acid sequences of proteins from gene sequences, the vast diversity of protein shapes and many factors that influence a protein’s 3D structure make it much more complicated to create simple folding rules that could be used to predict proteins’ structures from these sequences. Scientists have worked on this problem for nearly 50 years, and NIGMS has supported many of their efforts, including the Critical Assessment of Structure Prediction (CASP) program.

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A Focus on Microscopes: See Eye-Catching Images


Have you ever wondered what creates striking images of cells and other tiny structures? Most often, the answer is microscopes. Many of us have encountered basic light microscopes in science classes, but those are just one of many types that scientists use. Check out the slideshow to see images researchers have captured using different kinds of microscopes. For even more images of the microscopic world, visit the NIGMS Image and Video Gallery.

Visualizing Structures

Type of Microscope: Dark field
Used to Study: Living and dead cells

Oblong bacteria glowing blue on a black background.
Anthrax bacteria being killed by an agent that naturally glows blue when excited by ultraviolet light in the microscope.
Credit: Keiler Lab, Penn State University.

Type of Microscope: Time lapse
Used to Study: Living cells as they move over time

Cell-like compartments spontaneously emerge from scrambled frog eggs, with nuclei (blue) from frog sperm. Endoplasmic reticulum (red) and microtubules (green) are also visible.
A dividing cell of an African globe lily. This is one frame of a time-lapse sequence that shows cell division in progress.
Credit: Andrew S. Bajer, University of Oregon, Eugene.

Type of Microscope: Super resolution light
Used to Study: Activity in living cells

Oblong blue structures with red threads connected to them on the left and right.
DNA (blue) being pulled apart by microtubules (red) as a cell divides. The blue and red colors are due to the fluorescent label used to dye the sample.
Credit: Jane Stout and Claire Walczak, Indiana University.

Type of Microscope: Fluorescent light
Used to Study: Activity in dyed cells and molecules

Many spots and swirls of fluorescent green and purple.
Kidney tissue stained with fluorescent dyes that glow under high intensity light from the microscope.
Credit: Tom Deerinck and Mark Ellisman, NCMIR.

Type of Microscope: Confocal
Used to Study: 3D images of living cells

Round green-yellow structures with red edges and blue dots in their centers.
Cell-like compartments that spontaneously emerge from scrambled frog eggs, with nuclei (blue) from frog sperm.
Credit: Xianrui Cheng, Stanford University School of Medicine. Xianrui Cheng, James E. Ferrell Jr. SCIENCE 366: 631, 01 Nov 2019 (DOI: 10.1126/science.aav7793).

Type of Microscope: Electron
Used to Study: Dead cells

A circle containing many types of structures an inner circle that is clear.
Cross-section through the worm, C. elegans, revealing various internal structures frozen in time. This image was taken with transmission electron microscopy and labeled afterwards with color to highlight features in the image.
Credit: Piali Sengupta, Brandeis University.

Type of Microscope: Cryo-EM
Used to Study: Cellular components, particles (viruses, molecules, ribosomes)

An oblong capsule made up of tiny gray, yellow, and red structures.
The protein shell, or capsid, that surrounds HIV and is covered in a host protein (red), which allows the virus to evade detection.
Credit: Juan R. Perilla, Klaus Schulten, and the Theoretical and Computational Biophysics Group.

Explore Scientific Imaging Through a Virtual “Internship”

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Students, teachers, and other curious minds can step into a scientific imaging lab with a free online interactive developed by NIGMS and Scholastic. Imaging tools help scientists unlock the mysteries of our cells and molecules. A better understanding of this tiny world can help researchers learn about the body’s normal and abnormal processes and lead to more effective, targeted treatments for illnesses.

Entrances to the virtual imaging labs.
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Quiz: Prove Your Knowledge of Proteins!


Proteins play a role in virtually every activity in the body. They make up hair and nails, help muscles move, protect against infection, and more. Many NIGMS-funded researchers study the rich variety of proteins in humans and other organisms to shed light on their roles in health and disease.

Take our quiz to test how much you know about proteins. Afterward, find more quizzes and other fun learning tools on our activities and multimedia webpage, which includes an interactive protein alphabet.

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Pathways: The Imaging Issue

Cover of Pathways student magazine showing geometric shapes, pom-pom-like structures, and text that reads, Dive into the microscopic world. What do you think this image shows? Hint: It’s NOT an underwater scene! (Answer inside). Cover of Pathways student magazine.

NIGMS and Scholastic bring you our latest issue of Pathways, which focuses on imaging tools that help scientists unlock the mysteries of our cells and molecules. A better understanding of this tiny world can help researchers learn about the body’s normal and abnormal processes and lead to more effective, targeted treatments for illnesses.

Pathways is designed for students in grades 6 through 12. This collection of free resources teaches students about basic science and its importance to health, as well as exciting research careers.

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Through the Looking Glass: Microscopic Structures in Many Sizes


We seldom see microscopic objects next to one another, so it can be difficult to picture how they compare. For instance, it might surprise you that a thousand cold-virus particles could line up across one human skin cell! The largest objects that scientists view through microscopes are about a millimeter (roughly the size of a poppyseed), and they’re about 10 million times larger than the smallest molecules scientists can view: atoms.

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Freezing a Moment in Time: Snapshots of Cryo-EM Research


To get a look at cell components that are too small to see with a normal light microscope, scientists often use cryo-electron microscopy (cryo-EM). As the prefix cryo- means “cold” or “freezing,” cryo-EM involves rapidly freezing a cell, virus, molecular complex, or other structure to prevent water molecules from forming crystals. This preserves the sample in its natural state and keeps it still so that it can be imaged with an electron microscope, which uses beams of electrons instead of light. Some electrons are scattered by the sample, while others pass through it and through magnetic lenses to land on a detector and form an image.

Typically, samples contain many copies of the object a scientist wants to study, frozen in a range of orientations. Researchers take images of these various positions and combine them into a detailed 3D model of the structure. Electron microscopes allow us to see much smaller structures than light microscopes do because the wavelengths of electrons are much shorter than the wavelength of light. NIGMS-funded researchers are using cryo-EM to investigate a range of scientific questions.

Caught in Translation

One cluster that is yellow, purple, and orange and another that is beige, purple, and green. 3D reconstructions of two stages in the assembly of the bacterial ribosome created from time-resolved cryo-EM images. Credit: Joachim Frank, Columbia University.

Joachim Frank, Ph.D., a professor of biochemistry and molecular biophysics and of biological sciences at Columbia University in New York, New York, along with two other researchers, won the 2017 Nobel Prize in Chemistry for developing cryo.

Dr. Frank’s lab focuses on the process of translation, where structures called ribosomes turn genetic instructions into proteins, which are needed for many chemical reactions that support life. Recently, Dr. Frank has adopted and further developed a technique called time-resolved cryo-EM. This method captures images of short-lived states in translation that disappear too quickly (after less than a second) for standard cryo-EM to capture. The ability to fully visualize translation could help researchers identify errors in the process that lead to disease and also to develop treatments.

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Cool Images: The Hidden Beauty Inside Plants


Spring brings with it a wide array of beautiful flowers, but the interior structures of plants can be just as stunning. Using powerful microscopes, researchers can peek into the many molecular bits and pieces that make up plants. Check out these cool plant images from our Image and Video Gallery that NIGMS-funded scientists created while doing their research.

Several round structures that are yellow at the center and pink and purple around the edges and have honeycomb-like interiors. Credit: Arun Sampathkumar and Elliot Meyerowitz, California Institute of Technology.

In plants and 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. Cellular and molecular biologists frequently study Arabidopsis because it grows rapidly (its entire life cycle is only 6 weeks), produces lots of seeds, and has a genome that’s easy to manipulate.

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Twisting and Turning: Unraveling What Causes Asymmetry


Note to our Biomedical Beat readers: Echoing the sentiments NIH Director Francis Collins made on his blog, NIGMS is making every effort during the COVID-19 pandemic to keep supporting the best and most powerful science. In that spirit, we’ll continue to bring you stories across a wide range of NIGMS topics. We hope these posts offer a respite from the coronavirus news when needed.

Asymmetry in our bodies plays an important role in how they work, affecting everything from function of internal systems to the placement and shape of organs. Take a look at your hands. They are mirror images of each other, but they’re not identical. No matter how you rotate them or flip them around, they will never be the same. This is an example of chirality, which is a particular type of asymmetry. Something is chiral if it can’t overlap on its mirror image.

An image of a pair of hands, palms facing up. An arrow points to another image of the left hand on top of the right, both palms still facing up, illustrating that they can’t be superimposed. Our hands are chiral: They’re mirror images but aren’t identical.

Scientists are exploring the role of chirality and other types of asymmetry in early embryonic development. Understanding this relationship during normal development is important for figuring out how it sometimes goes wrong, leading to birth defects and other medical problems.

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