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HAdV Attachment Receptors for which we have structural data on binding with the virus. Five different structures, all attached to the cell memberane from the outer side. The viral protein remains very similar in all five cases, but the proteins take very different shapes. The sugars are much smaller than the proteins.

Reading Our Review: Structural Biology of Human Adenovirus Binding to Receptors

Hello again,

my name is Aleksandra Stasiak, and my PhD project concerns human adenovirus binding to integrins. If you want to know more about it, why and how I am doing it, you can read my previous blog post “Tracking Adenovirus Binding in Tuebingen”. This time, I am going to explain an article we have recently published, in less technical terms for a more general audience.

Reading a Review – What is a review anyway?

Do you ever feel when reading about science that you do not understand, and you are not even sure what it is you do not understand? Well, that’s actually normal, and it’s not just you. Getting into a new scientific field is challenging for everyone, also scientists. Every field operates with its specific, precisely-defined vocabulary (just ask a virologist about the difference a virus-permissive and a virus-susceptible cell, if you dare), and larger models or assumptions based on years of completed research. To get up to speed, there are popular science publications for laypeople, which aim to explain this bird eye’s view of a field in an engaging, clear manner. Scientists have their own version of this – it is called a review article.

What is the use of a review?

A review article is generally just a bit less engaging than a popular science article – after all, the assumption is that the reader wants to know the contents and will keep on reading. A review tells a scientist new to the field (like an undergraduate student, or someone starting a new research project), what we already know and still need to discover. Also, scientists who work in this area get a new perspective by taking a step back to look at the general direction the research is following. Moreover, both kinds of reader can easily find a list of important research papers in the references, which saves them time.

Recently, my supervisor and I have published a review article. The title of the article is “Human adenovirus binding to host cell receptors: a structural view”. You can read it here.

What is it about?

Our review is about what structural biologists have discovered about human adenovirus (HAdV) interactions with its receptors in recent years. I have already explained why it is useful and interesting to study HAdV in my previous blog post. Briefly, it may cause many different kinds of disease, but it could also be a tool in vaccines, cancer and gene therapy, helping us to cure or prevent some of the scariest diseases.

I have also written about structural biology, a branch of biology that establishes shapes of biological molecules, mostly proteins. By finding out the arrangement of atoms within a protein, or multiple interacting proteins, we can understand which atoms in the protein are crucial for their interactions. Thanks to this, we can design drugs to prevent the interaction – for instance a virus attaching to a cell. We can also understand why certain changes (mutations) in proteins cause disease and design treatments to counteract them.

Receptors

In my previous post, I have written that receptors are proteins on the surface of the cell, to which a virus attaches or uses to enter the cell. Actually, other molecules on cell surface can serve as receptors too: for instance, sugars or lipids. For a virus, being able to find and attach to its receptor is crucial. Only once it has attached to the cell can it enter it and begin the process of infection. That is why it is so important for us to study them, so we understand what we can disrupt to prevent infection.

What did we write?

The goal of our review was to go through all the structural information we have on how HAdVs interact with their receptors and what new things researchers have discovered over the past few years. Our research group described the binding of two different sugars, and another that of a different protein receptor. Some of these are particularly interesting, because they bind non-symmetrically to a symmetric virus protein.

The virus protein, the knob, which sticks away from the surface of the virus, is a homotrimer. This means, it is composed of three identical parts. Usually, we expect that there is one receptor-binding site per part, so there would be three in total. Therefore, we would have three receptors binding to each knob. Some of the receptors we describe at the beginning are like this. However, recently, researchers have described different types of binding. In some cases, the protein is so big, only one or two copies can bind to the sites easily, and the others remain unoccupied. In another case, a single sugar molecule can bind to two sites at the same time, which leaves the third one free. These non-symmetrical binding modes are quite surprising and we did not expect them.

Why is adenovirus binding important?

Discoveries like those ones matter, because they change the way we think about virus binding. For instance, if we know that a sugar binds to two out of three sites, we understand why it binds more strongly than we would expect if it only bound to one site as usual. This way, we can also design drugs that will bind even more strongly, by binding to all three sites. Moreover, this changes the way we think and helps us with solving structures of other non-symmetrical binding types.

Open Access Availability – You can read it too!

The title of the article is “Human adenovirus binding to host cell receptors: a structural view”. It is available in open access, which means anyone can read it here. One of our goals in VibrANT is for our publications to be available to everyone. This means the public can freely read what happens to the money of EU taxpayers. The purpose of this blog is to make it easier to understand what we often write about in very technical terms in the research papers.

More Papers from ViBrANT

Our review is just one of many papers written and published by ViBrANT participants. Last year, a special issue of the journal, devoted to our ITN, came out. Multiple reviews and opinion pieces written by the PhD students, their supervisors, and colleagues, can be found here. They cover topics related to the research of our network.

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