Jan Steyaert Lab

Research focus

Nanobody-enabled Structural Biology

Published work of the Steyaert lab (see www.steyaertlab.eu for all details) established that the antigen binding fragments of Camelid heavy chain only antibodies - known as Nanobodies (Nbs)- constitute unique research tools in structural biology. By rigidifying flexible regions and obscuring aggregative surfaces, Nanobody complexes warrant conformationally uniform samples that are key to protein structure determination by X-ray crystallography or cryo-EM. We make and use nanobodies to investigate enzymes, membrane proteins and protein complexes that are involved in signal transduction. We focus on conformationally complex systems that have been resistant to structural investigation by conventional methods.

Locking GPCR conformational states. The active-state conformations of G Protein Coupled Receptors (GPCRs) are unstable in the absence of specific cytosolic signaling partners representing key challenges for structural biology. We developed conformational Nanobodies against the β2 adrenergic receptor, the muscarinic acetylcholine receptor and the μ-opoid receptor that exhibit G protein-like behavior, and obtained the first agonist-bound, active-state crystal structures of these receptor●Nb complexes.

Stabilizing transient signaling complexes. We developed nanobodies that stabilize the β2AR●Gs complex and others that bind to Vps34 complex II. These antibodies were instrumental for obtaining crystal structures of these key transient multiprotein assemblies, providing the first structural view on GPCR transmembrane signaling and on the regulation of autophagy, respectively.

Unveiling conformational states of membrane transporters and ion channels. Functional understanding of membrane transporters and ion channels requires the structural characterization of different conformational states. Our lab produces Nanobodies to lock and solve the structures of key functional conformations of several transporters and ion channels by X-ray crystallography.

Investigating the mechanism and regulation of complex GTPases. Guanine nucleotide binding proteins are regulatory hubs in nearly all cellular processes. While the small GTPases of the Ras superfamily have been relatively well characterized, the mechanism of complex multi-domain GTPases is much less established. The Versées lab studies the mechanism and regulation of particular complex GTPases that are implicated in bacterial virulence and persistence or have been linked to Parkinson disease and epilepsy.

Founding ConFoTherapeutics. We transferred know-how and IP to ConFo Therapeutics, a new spin off company that exploits the conformational complexity of therapeutic targets for better drug discovery.

Publications

Skywalker-TBC1D24 has a lipid-binding pocket mutated in epilepsy and required for synaptic functionFischer B* Lüthy K* Paesmans J* De Koninck C Maes I Swerts J Kuenen S Uytterhoeven V Verstreken P* Versées W*NATURE STRUCTURAL & MOLECULAR BIOLOGY, 23, 965-973, 2016* These authors contributed equally
Structural insights into micro-opioid receptor activationHuang W* Manglik A* Venkatakrishnan A Laeremans T Feinberg E Sanborn A Kato H Livingston K Thorsen T Kling R Granier S Gmeiner P Husbands S Traynor J Weis W Steyaert J Dror R Kobilka BNATURE, 524, 315-21, 2015* These authors contributed equally
Structure and flexibility of the endosomal Vps34 complex reveals the basis of its function on membranesRostislavleva K* Soler N* Ohashi Y Zhang L Pardon E Burke J Masson G Johnson C Steyaert J Ktistakis N Williams RSCIENCE, 350, aac7365, 2015* These authors contributed equally
Structure of a prokaryotic fumarate transporter reveals the architecture of the SLC26 familyGeertsma E Chang Y* Shaik F* Neldner Y Pardon E Steyaert J Dutzler RNATURE STRUCTURAL & MOLECULAR BIOLOGY, 22, 803-8, 2015* These authors contributed equally
Crystal structure of the beta2 adrenergic receptor-Gs protein complexRasmussen S, Devree B, Zou Y, Kruse A, Chung K, Kobilka T, Thian F, Chae P, Pardon E, Calinski D, Mathiesen J, Shah S, Lyons J, Caffrey M, Gellman S, Steyaert J, Skiniotis G, Weis W, Sunahara R, Kobilka BNATURE, 477, 549-55, 2011

News

Scientists track down possible new treatment for epilepsy

26/09/2016 - Increasing the concentration of specific fats in the brain could suppress epileptic seizures. This is evident from ground-breaking research carried out by groups of Patrik Verstreken (VIB-KU Leuven) and Wim Versées (VIB-Vrije Universiteit Brussel).

New biotech company Confo Therapeutics launched by VIB and Vrije Universiteit Brussel: Capricorn Venture Partners leads 1st financing round of € 3 million

24/06/2015 - The establishment of Confo Therapeutics, a spin-off of VIB and Vrije Universiteit Brussel, was announced today. A consortium led by Capricorn Health-Tech Fund with the participation of Qbic and SOFI.

Interview with Brian Kobilka and Jan Steyaert

18/12/2014 - ​Brian Kobilka shared the 2012 Nobel Prize in Chemistry with Robert Lefkowitz. A couple of months ago Kobilka was in Brussels to give a talk about his work on invitation of Jan Steyaert (VIB/Vrije Universiteit brussel).

VIB researchers involved in Brian Kobilka’s Nobel-prizewinning research

10/10/2012 - Jan Steyaert and his colleagues were involved in the groundbreaking work in which Brian Kobilka’s research team discovered the structure of these receptors.

Both Nature and Science select VIB-VUB research as 2011 highlights

04/01/2012 - Great news to start 2012. Top journals Nature and Science are featuring research from VIB researchers at Vrije Universiteit Brussel in their 2011 highlights.

Common drugs initiate a molecular pas de quatre at the surface of the cell membrane

25/07/2011 - In a Nature article, an international consortium reveals the complete 3D structure of an activated GPCR (beta-2AR) in a complex with its G protein. The Jan Steyaert Lab (VIB-VUB) produced the Xaperone™ that holds these proteins together.

Adrenaline receptor ‘frozen in action’ by VIB researchers - Discovery means breakthrough for the development of new drugs based on GPCR’s

12/01/2011 - Using tiny antibodies, dubbed Xaperones (TM), scientists from VIB and Vrije Universiteit Brussels collaborated in elucidating the structure of the adrenaline receptor - a scientific first with possibly profound implications for drug development.

Jan Steyaert

Jan Steyaert

Research area(s)

Bio

​​PhD: Vrije Universiteit Brussel, Belgium, 1991
Postdoc: ILRI, Nairobi, Kenya, 1993-94
VIB Group leader since start VIB (1995)
Associate Department Director since 2012

Contact Info

VIB-VUB Center for Structural BiologyBuilding EPleinlaan 2 1050 BRUSSELRoute description