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Electron Holography Produces First Image of a Single Protein

A non-destructive method for imaging single proteins could help solve one of the biggest challenges in biology

The behaviour and function of proteins is largely determined by their shape.  So one of the great ongoing quests in biology is to understand and model the structure of proteins. 

That’s a tricky task. Biologists currently do it using techniques such as X-ray crystallography, which requires millions of protein chains to form into a crystal.  The trouble is that most proteins don’t form crystals. And even when they do, not all the molecules will be in the same conformation and so the diffraction pattern can end up being a kind of average of several different shapes.

That’s why biologists know the shape of less than 2 per cent of the proteins in humans.

What’s needed, of course, is a way of imaging individual proteins. One idea is to us x-rays or electron beams to do the trick and indeed some groups have had some success with this technique. But the disadvantage is that beams with an energy of a few KeV tend to destroy biomolecules so it’s not clear how accurate these images can be. Nether is it possible to view the molecules over time.

Today, Jean Nicholas Longchamp and pals at the University of Zurich in Switzerland have found a way round this. These guys make the entirely sensible suggestion of imaging proteins using low energy electron beams that don’t destroy biomolecules. 

At this energy, electron beams have a wavelength of a nanometre or so, making them perfect not just for imaging with atomic resolution, but for holography. 

And that’s exactly what these guys have done. They’ve created an electron hologram of a protein molecule called ferritin–that’s the football-shaped protein that stores and releases iron and is found in almost all living things.

The technique is fairly straightforward. They mix ferritin and carbon nanotubes in water which they then allow to evaporate. This leaves carbon nanotubes with single ferritin proteins bonded to them.

The evaporation takes place in a sieve-like container and leaves some of the ferritin-carrying nanotubes suspended across the holes in the sieve. That allows Longchamp and co to send the low energy electron beam from one side of the hole and then record the interference pattern on the other. 

The result is the first atomic resolution electron hologram of ferritin ever made in a non-destructive way. “We have reported the very first non-destructive investigation of an individual protein by means of  low-energy electron holography,” they say.

They’ve even compared their images to ones of ferritin imaged with high energy electrons and are able to show the damage that the high energy bombardment causes.

That’s exciting news. The problem of accurately determining the structure, and therefore the function, of proteins is a major headache for biologists and one that low energy electron holography could help to solve quickly. “The sample preparation method can be applied to a broad class of molecules,” say Longchamp and friends.

They now want to improve the resolution of their technique and have a number of tricks up their sleeves that they are no doubt investigating.

Given that the techniques is relatively straightforward and inexpensive, expect to see an explosion of interest in single molecule structural biology at atomic resolution.

Ref: Non-Destructive Imaging Of An Individual Protein

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