Biophysical Society Thematic Meeting | Bucharest 2026

Biophysics of Membrane Reactions in Brian

Tuesday Speaker Abstracts

UNDERSTANDING PROTEIN-PROTEIN AND PROTEIN-MEMBRANE INTERACTIONS IN THE PLEXIN TRANSMEMBRANE RECEPTOR FOR AXON GUIDANCE: A PERSPECTIVE FROM STRUCTURAL BIOLOGY, BINDING BIOPHYSICS AND MOLECULAR DYNAMICS SIMULATIONS AS WELL AS AI BASED MODELING Matthias Buck Case Western Reserve University, USA Plexin-family receptors play a crucial role in guiding cell migration during cardiovascular and neuronal development, as well as in disease and regeneration processes of these systems. Understanding plexin receptors at the molecular level is critical for the development of drugs to target diseases such as Alzheimer’s and various cancers. In my seminar I will first provide an overview of the system and summarize some of the contributions of the Buck lab. over the last 20+ years to the biochemical, biophysical and structural characterization of the intracellular regions of plexin-B1 in particular. This will emphasize the discovery of a novel Rho GTPase binding motif and the formation of Rho GTPase – plexin complexes, which can be viewed as dynamic protein-protein complex. Recently, we discovered another novel region in plexins that strongly interacts with Rho GTPases. Yet, it is still unclear how binding to these regions impacts the molecular mechanism controlling plexin activity. Our preliminary data suggest that interactions between Rho GTPases and plexin generally inhibit plexin function. This inhibition appears to be the default state unless the proteins are localized at a plasma membrane (PM)-like environment enriched with specific lipids that counteract these interactions. The project utilizes biophysical binding assays, solution NMR, x-ray crystallography and computational modeling, as well as recently FRET/PIE-FCCS and hydrogen-deuterium exchange mass spectrometry (HDX-MS). A second aspect of the system concerns the single transmembrane (TM) helix this receptor and its co-receptor uses to cross the lipid bilayer and to transmit signals between its extra- and intracellular regions. The TM helices typically dimerize and do so in configurationally distinct states which are thought to correspond to different states of activity. I will also mention the planned work on this part of the protein which is part of my sabbatical JSPS fellowship in Prof. Hiroaki Suga’s lab. at Tokyo Univ. in collaboration with the Tagaki lab. at Osaka Univ.

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