Magnus Kjærgaard on Tethered Enzymes, Multivalent Interactions—and Tigers

Avinash Patel
Avinash Patel

Group Leader, Discovery Biology, Dewpoint Therapeutics

Type Kitchen Table Talk

On April 23, Dewpoint was pleased to welcome Magnus Kjærgaard, assistant professor and team leader at the Danish Research Institute of Translational Neuroscience, as part of our Kitchen Table Talks series.

We often think the specificity of a kinase’s activity comes through its catalytic domain and its subcellular positioning in space and time. However, Magnus’s recent studies show that for kinases that have an IDR, the length of the IDR modulates the Michaelis–Menten kinetics of their activity.

Additionally, Magnus spoke about how intrinsically disordered linkers control avidity in multivalent protein interactions.

Both of his stories have interesting implications in thinking about the role of condensates in cell biology. Check out the video for more on that, and a little bit about tigers.

Magnus Kjærgaard on Tethered Enzymes, Multivalent Interactions—and Tigers

Create an Account or Sign In to view the video.

Avinash Patel (00:00:05):
It’s nice to meet you Magnus. Well we met over Twitter so that’s the power of social media these days and what really caught my attention was basically the tweet that Magnus had, that said that “we quite are interested in kinases, we know how kinases get their specificity through their catalytic domain or where they are present in the cell at a given space and time.” But what Magnus said was basically that many kinases might have interesting disordered parts and those disordered linker regions actually and then can regulate the Michaelis-Menten kinetics of phosphorylation of kinases. That I found really, really interesting and I sent the paper over to Mark and Diana and they said that we should have Magnus over to tell us more about it. And additionally he also said how he is interested, and did some studies in finding out, how these disordered linkers also control the avidity of protein-protein interactions. So both the kinase part and the protein interactions in complexes part are intrinsically connected to our interest in condensates, so we are really looking forward to that. Magnus is assistant professor in the Department of Molecular Biology and Genetics in Aarhus University and also a team leader in the Research Institute of Translational Neuroscience. Is that right Magnus?

Magnus Kjærgaard (00:01:45):
Yeah that’s right.

Avinash (00:01:49):
And has started since 2016 and we look forward to your talk now. Thank you.

Magnus Kjærgaard (00:01:56):
Great. Yes, thank you very much for having me. As Avi mentioned I’ll be talking about intrinsically disordered linkers and how they regulate biochemistry, which is one of the main interests of my research group. Before we get started I would just like to take the opportunity to shamelessly to plug our new upcoming seminar series on intrinsically disordered proteins that is organized by me and Alex Holehouse and we’ll be starting, first day in two weeks because we don’t want to compete with the IDPSIG group for an audience.

Magnus Kjærgaard (00:02:34):
Before we get to the science, I would like to start out by acknowledging the people who actually do the work. So the work that I’m going to talk about has been done by these three fantastic postdocs. So the tethered phosphorylation kinetics is done by Mateusz. Charlotte has done the work on measuring effective concentrations using a fluorescent biosensor and has also participated in the avidity projects and Agnieszka has done all the avidity measurements. And I promised Matty to tell you that he’s actively looking for a job, so if you like what you see then you know where to get more. Great.

Magnus Kjærgaard (00:03:24):
So this takes us to the science bit and I promised to talk on intrinsically disordered linkers, but I would actually like to start somewhere else. I would like to start out by talking about the related subject of tigers. More specifically, I would like you to consider what my risk is of being eaten by a tiger today. And you may justifiably think that this is an extraordinarily stupid question to start our seminar out considering. And you’d be right. And the reason for that is, of course, that the risk is extremely low because being eaten by a tiger is equivalent to what we in the molecular world would call a bimolecular reaction. So in order for the reactants to react they first have to physically meet and for a bimolecular reaction this is concentration dependent. And so the chance of me being eaten by a tiger is extraordinarily low, not because I wouldn’t be a good tiger snack or the tiger wouldn’t be a good predator, but because the concentration of tigers in Denmark is very, very low…

Join the conversation

Create an Account or Sign In to comment.