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.


A homologue of the Parkinson's disease-associated protein LRRK2 undergoes a monomer-dimer transition during GTP turnoverDeyaert E* Wauters L* Guaitoli G Konijnenberg A Leemans M Terheyden S Petrovic A Gallardo R Nederveen-Schippers L Athanasopoulos P Pots H Van Haastert P Sobott F Gloeckner C Efremov R Kortholt A Versées WNature Communications, 8, 1008, 2017* or °: authors contributed equally
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* or °: 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* or °: 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* or °: 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* or °: authors contributed equally

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18 of the world’s most influential researchers at VIB

20/11/2019 - Each year, Clarivate analytics identifies the world’s most influential researchers who have been cited most frequently by their peers over the last decade. No less than 18 VIB researchers are part of this highly acclaimed group of influential scientists.

How do carrier proteins transport ADP and ATP in and out of mitochondria?

08/01/2019 - Scientists at the MRC-MBU in Cambridge, UK have discovered how a key transport protein, called the mitochondrial ADP/ATP carrier, transports adenosine triphosphate (ATP), the chemical fuel of the cell.

Megabodies: a new tool for innovative applications in research and drug discovery

03/01/2019 - The Jan Steyaert lab at the VIB-VUB Center for Structural Biology developed an innovative plug and play technology to rigidly graft functional Nanobodies® on several scaffolds with diverse properties to build Megabodies.

Research center for high-resolution electron cryogenic microscopy to open

21/09/2018 - The Center for Structural Biology (VIB-VUB), headed by Professors Jan Steyaert and Han Remaut officially opened the ‘international facility for Bio Electron Cryogenic Microscopy’ (BECM) at the VUB Campus in Brussels.

Newly described process in Parkinson’s protein as a potential new therapy route

18/10/2017 - ​An international group of researchers led by Professor Wim Versées (VIB-VUB) has unraveled the workings of an essential mechanism in ‘Parkinson’s protein’ LRRK2.

Wim Versées receives Michael J. Fox Foundation grant for investigating Parkinson’s disease-associated protein

20/05/2017 - ​Wim Versées, staff scientists at the VIB-VUB Center for Structural Biology, received a Michael J. Fox Foundation grant. The foundation provides funding for translational and clinical research supporting Parkinson’s-related breakthroughs.

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).

Jan Steyaert

Jan Steyaert

Research area(s)


​​PhD: Vrije Universiteit Brussel, Belgium, 1991
Postdoc: ILRI, Nairobi, Kenya, 1993-94
VIB Group leader since start VIB (1995)
Associate Department Director since 2012
VIB Science Director since 2017

Contact Info

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