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Researchers locate the body's largest cell receptor

January 03, 2019

"What we're looking at is evolution at a structural level. A receptor with a toadstool structure that stems from way back and the common ancestors of insects and humans..."

A receptor that is a 'recipient' for the absorption of vitamin B12 is what he is talking about here - Associate Professor, PhD Christian Brix Folsted Andersen from the Department of Biomedicine at Aarhus University in Denmark. Vitamin B12 is the vitamin that we - even with a healthy diet - most often lack which in turn can lead to serious anaemic diseases and symptoms from the central nervous system.

Working together with his research group, Christian Brix Folsted Andersen has now described the body's largest cell receptor: A mysterious prehistoric construction that 'back in the day' was created by the meeting of two proteins and which - for reasons we do not yet understand - is preserved in what is in molecular terms a colossal structure that has never been seen before. In the 1960s, the female scientist Dorothy Hodgkin received the Nobel Prize for her scientific breakthrough in determining the structure of the B12 vitamin. Now we are also aware of the more than one thousand times larger receptor structure which the B12 vitamin is completely dependent on and which enables it to be absorbed in the body.

The research results which have recently been published in the scientific journal Nature Communications, shed fundamental light on the issue of why people in some cases have problems with vitamin B12 absorption and lose nutrients in the kidneys.

"With the help of x-ray crystallography, we've succeeded in determining how the receptor is able to organise itself in a previously unknown way in human biology. With this new knowledge we're finally able to explain why thousands of people around the world with specific genetic changes are unable to absorb the vitamin," explains Christian Brix Folsted Andersen over the phone from the University of Washington in USA.

"But in my mind, the most interesting aspect is that with the help of advanced electron microscopy, which I'm learning about in detail here in Seattle, we have been able to see how the receptor as a whole looks and thus also see how the receptor absorbs the B12 vitamin in the intestines and various other substances in the kidneys. It's fantastic to have the opportunity to see this as the first person ever," he says.

Christian Brix Folsted Andersen points out that in an evolutionary context, there is something very mysterious about the receptor as it does not resemble anything seen previously.

"At the same time, by comparing genes we can see that the receptor has the same structure as we find in insects and that it must have been evolved very early in evolution - many millions of years ago and thus long before the origin of mammals," he says.

Christian Brix Folsted Andersen's research is a continuation of his long-standing work together with Søren K. Moestrup into B12 transport. In 2010, this research led to new and pivotal knowledge about how the receptor specifically recognises B12 in the small intestine.

"The research we're carrying out today is a continuation of decades of research into the vitamin B12. Indeed, twenty-five years ago we had no idea about what was going on the shadowy recesses of the intestines. Now the lights have been turned on and we can see how it all works in a way that none of us could have imagined," says Søren K. Moestrup.

"Apart from obviously being very satisfying from a scientific viewpoint, it also opens completely new perspectives for medical treatment. For example, we now have in-depth knowledge about a receptor that could evidently be used to transport drugs into the kidneys and intestines," he says.

Aarhus University

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