News
Our preprint Stereoselectivity and functional plasticity of a common ligand-binding pocket in TRPM3 is published on bioRxiv.
Using cryo-EM and electrophysiology we discover that chemically different plant-derived and synthetic antagonists and agonists of TRPM3 act on the same binding pocket. We report that mutations within this promiscuous ligand binding pocket, including novel gain-of-function patient mutations, can alter the stereoselectivity and, in some cases, invert the functional outcome of ligand binding, with important consequences for TRPM3-targeted drug discovery and therapy. We further describe in detail the binding geometry of primidone, an anticonvulsant and barbiturate congener, used in the treatment of epilepsy. This could serve as a starting point for the rational design of more potent drugs to modulate TRPM3.
Our paper Structures of native SV2A reveal the binding mode for tetanus neurotoxin and anti-epileptic racetams is out in Nature communications.
In this study we provide evidence for SV2A as the protein-receptor for Tetanus Neurotoxin (TeNT) and deliver the structural basis for TeNT entry into central neurons. We unveil the precise geometry of TeNT binding to dipartite SV2-ganglioside receptors substantiating the dual-receptor hypothesis. Further, SV2A is the target for the major anti-seizure drug Levetiracetam used in the treatment of epilepsy for which we solved a drug-bound SV2A structure.
The preprint MISO: Microfluidic protein isolation enables single particle cryo-EM structure determination from a single cell colony is published on bioRxiv.
In this study a microfluidic device to isolate proteins from ultralow amounts for cryo-EM is described and named MISO. We have supported the Efremov lab with mammalian membrane proteins TMEM16F and TMEM206 and compared the method with conventional purification and cryo-EM workflows.
Johanna Zipf joins the group as a PhD student
A summer school student joined our lab activities for four days and gave a helping hand
Hadrien successfully defended his Master thesis. Congratulations!
Alexander Shkumatov joins the group as an innovation scientist
Janine receives an FWO Junior Project Fundamental Research grant. We are excited and thankful to FWO for the support.
A summer school student joined our lab activities for four days and gave a helping hand
Cryo-EM structures of a LptDE transporter in complex with Pro-macrobodies offer insight into lipopolysaccharide translocation is out at Nature communications.
This work provided the structural basis for LPS export to the outer bacterial membrane through visualization of the LptDE transporter ensemble in open and closed state by Cryo-EM. For this, Pro-macrobodies, rigid analogues of macrobodies and potent fiducial markers in cryo-EM, have been developed and applied in this study.
Hadrien Letourneur joins the lab as a master student
Our mammalian cell culture room is established and fully functional.
Our paper Structural basis for ion selectivity in TMEM175 K+ channels is published in eLife.
In this study we set out to provide first structural insight into a novel class of potassium channels on lysosomes. In combination with electrophysiology, high-resolution X-ray structures detailed how gating and potassium selectivity in the TMEM175 family is conferred through a hitherto unknown selectivity filter. High-resolution structures have been obtained through the development of a novel crystallization chaperone (macrobody) made of a nanobody fused to maltose binding protein (MBP).