Lecture
L(SB)2 Seminar: Conformational regulation of the GTPase-interacting ubiquitin ligase HACE1
- Date
- Wednesday 11 June 2025
- Time
- Location
-
Gorlaeus Building
Einsteinweg 55
2333 CC Leiden - Room
- CM.3.23
Abstract
The ubiquitin system is a principal regulator of cellular signaling in eukaryotes, deregulation of which is linked to manifold diseases pathways. It is therefore pivotal that the actions of the ubiquitination machinery are tightly controlled and specific. My research group explores the structural mechanisms underlying this specificity, focusing on the substrate-recruiting class of ubiquitin ligases (E3 enzymes). In my talk, I will feature our recent discoveries on the human HECT-type ligase HACE1, a tumor suppressor, with additional, poorly understood functions in neurodevelopment. HACE1 regulates distinct aspects of membrane dynamics through interactions with small GTPases, including RAC1 and selected members of the RAB-family. Our results provide a structural framework for understanding HACE1 regulation and substrate specificity, indicating a critical influence of the macromolecular context on ligase function.
The L(SB)2 seminars is a new seminar series that aims to bring together all researchers in Leiden that are interested in biophysics and structural biology. L(SB)2, the Leiden Seminars in Biophysics and Structural Biology, takes place monthly and combines presentations of talented PhD students from Leiden University with talks of PIs from other Dutch or international universities. We hope to see many of you there!