Nobel Prize in Chemistry Awarded for 3D Views of Biological Molecules

Figuring out the shape of a protein is crucial to figuring out its function. The structure of a virus, for instance, gives essential clues to how it invades a cell. For decades, the main method for studying protein structure was stacking many copies of a protein into a crystal, bouncing X-rays off the crystal and then deducing the protein shape using the patterns of X-ray reflections.

But many proteins, especially those embedded in the outer membranes of cells, are too floppy or disordered to crystallize.

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How eight winners got the word.

Dr. Henderson, of the MRC Laboratory of Molecular Biology in Cambridge, England, started his career as an X-ray crystallographer. Stymied by the limitations, he turned to a different instrument, the electron microscope.

Electron microscopes were invented in 1931. But they operate in a vacuum and bombard samples with electrons, so they are ill-suited for studying proteins and other biological molecules. They dried the samples and damaged them with radiation.

For the particular protein that Dr. Henderson and his colleagues wanted to study, embedded in the membrane of a photosynthesizing organism, the vacuum was not an insurmountable problem. They left the protein embedded in the membrane and protected it with a glucose solution to prevent it from drying out.

They also turned down the intensity of the electron beam and took advantage of the regular arrangement of the proteins in the membrane. That allowed Dr. Henderson, in 1975, to reconstruct the shape of the protein from the scattering of the electrons, almost the same mathematical analysis he had used for X-ray crystallography.

For most proteins, scientists could not rely on a protein being embedded in a regular pattern, all oriented in the same direction. Dr. Frank, of Columbia University, came up with the next advance honored by the Nobel committee. He recorded images of many copies of a protein at one-time, scattered in random orientations. A computer grouped together similar images — the proteins that were in similar orientations — and combined them to produce a sharper result. From the combined orientations, he was also able to put together the three-dimensional shape.


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Dr. Dubochet, of the University of Lausanne, Switzerland, further refined the technique — quick-freezing the molecules to protect them from the vacuum. But in ice, water molecules usually stack into a crystal shape, and the bouncing of electrons off the ice crystals in a frozen sample resulted in useless images.

To overcome this problem, Dr. Dubochet dipped the samples in liquid nitrogen-cooled ethane. At minus 321 degrees Fahrenheit (minus 196 Celsius), the water molecules froze so quickly that they had no time to line up in crystals, solidifying instead into a random structure, more like glass. That enabled the electron microscope technique to view the embedded proteins instead of the ice.

Why is the work important?

The technique is already driving some scientific advances. Last year, scientists were able to use cryo-electron microscopy to analyze the structure of the Zika virus, the mosquito-borne virus that causes birth defects. The same technique was used to figure out the structure of proteins involved with circadian rhythms, advances that were recognized with this year’s Nobel Prize in Medicine.


From left, Dr. Dubochet, Dr. Frank and Dr. Henderson.

From left: University of Lausanne, Columbia University and Cambridge University, via European Pressphoto Agency

Who are the winners?

Jacques Dubochet, 75, is a Swiss citizen. He retired from the University of Lausanne in Switzerland in 2007. His web page at the university humorously notes that in October 1941, he was “conceived by optimistic parents” and in 1946 he was “no longer scared of the dark, because the sun comes back.” He noted of his dyslexia: “This permitted being bad at everything … and to understand those with difficulties.”

Joachim Frank, 77, was born in Germany and is now a citizen of the United States. He is a professor of biochemistry and molecular biophysics Columbia University in New York. He is also an investigator for the Howard Hughes Medical Institute and a member of the National Academy of Sciences. In 2014, he received the Benjamin Franklin Medal in Life Science from the Franklin Institute in Philadelphia.

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Richard Henderson, 72, was born in Scotland and is a British citizen. He has worked at the British Medical Research Council’s Laboratory of Molecular Biology in Cambridge since 1973. He served as the laboratory’s director from 1996 to 2006.

Who else has won a Nobel this year?

■ Jeffrey C. Hall, Michael Rosbash and Michael W. Young were awarded the Nobel Prize in Physiology or Medicine on Monday for discoveries about the molecular mechanisms controlling the body’s circadian rhythm.

■ Rainer Weiss, Kip Thorne and Barry Barish received the Nobel Prize in Physics on Tuesday for the discovery of ripples in space-time known as gravitational waves.

Who won the 2016 Chemistry Nobel?

Jean-Pierre Sauvage, J. Fraser Stoddart and Bernard L. Feringa were recognized for their development of nanomachines, made of moving molecules, which may eventually be used to create new materials, sensors and energy storage systems.


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When will the other Nobels be announced?

Three more will be awarded in the days to come:

■ The Nobel Prize in Literature will be announced on Thursday in Sweden. Read about last year’s winner, Bob Dylan.

■ The Nobel Peace Prize will be announced on Friday in Norway. Read about last year’s winner, President Juan Manuel Santos of Colombia.

■ The Nobel Memorial Prize in Economic Science will be announced on Monday, Oct. 9, in Sweden. Read about last year’s winners, Oliver Hart and Bengt Holmstrom.

Liam Stack contributed reporting from London.

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