Keio University Human Biology-Microbiome-Quantum Research Center (WPI-Bio2Q) will hold a seminar as follows.
This is an event for faculty, students, and staff of Keio University.

Understanding biology by cryoEM analysis -AI-based design, toxin, in-situ structure etc –

Date & Time: 15:00 -17:00, July 24, 2026

Venue: 3F Meeting room, Center for Integrated Medical Research, Shinanomachi Campus, Keio University

Onsite only / No pre-registration required

Speaker 1:
Atsushi Yamagata, PhD
Senior Scientist, Laboratory for Protein Function and Structural Biology RIKEN Center for Biosystems Dynamics Research , Yokohamal, Japan

Title:
“Structural Insights into the Synaptic Targeting Mechanisms of Botulinum Neurotoxin and Racetam-Based Antiepileptic Drugs”

Abstract:
Synaptic vesicle glycoprotein 2A (SV2A) is an abundant membrane protein in synaptic vesicles, although its physiological function remains poorly understood. It serves as a receptor for botulinum neurotoxins and as the molecular target of the antiepileptic drugs levetiracetam (LEV) and brivaracetam (BRV).
We determined the cryo-electron microscopy (cryo-EM) structures of SV2A in complex with the receptor-binding domain of botulinum neurotoxin A2 (BoNT/A2 Hc), as well as with LEV and BRV. Botulinum neurotoxin recognizes the luminal domain of SV2A through both protein–protein and protein–glycan interactions. LEV and BRV bind to the putative substrate-binding pocket in the outward-open conformation of SV2A. Using a newly developed label-free spectral shift assay, we further demonstrated that van der Waals interactions between the propyl group of BRV and SV2A are responsible for the higher binding affinity of BRV over LEV.
In this presentation, I will describe these structural studies and our recent efforts to elucidate the physiological functions of the SV2 family using proximity-dependent biotin identification (BioID). In addition, I will introduce our ongoing AI-driven binder design project targeting SV2A for the visualization of synaptic density.

Speaker 2:
Reiya Taniguchi, PhD
Team director, Laboratory for in situ Structural Biology RIKEN Center for Integrated Medical Sciences (IMS), Yokohama, Japan

Title:
“Visualizing the structural heterogeneity of the nuclear pore complex with cryo-ET”

Abstract:
Cryo-electron tomography (cryo-ET) is a technique for visualizing three-dimensional architecture of frozen biological specimens by computationally reconstructing volumes from a series of two-dimensional projection images acquired at multiple tilt angles. Combined with cryo-focused ion beam milling, cryo-ET has become a powerful tool for analyzing the structures of macromolecular complexes directly inside cells or tissues. Moreover, recent advances in image processing have enabled detailed analyses of the structural heterogeneity among particles in situ.
In this talk, I will present our in situ cryo-ET analysis of the nuclear pore complex (NPC) in mouse embryonic stem cells, which uncovered unexpected structural heterogeneity among NPC particles. Using fluorescence imaging as a complementary approach, we obtained insights into the functional significance of the NPC architecture in maintaining nuclear envelope integrity. This work highlights the strength of cryo-ET for analyzing the structural heterogeneity of macromolecular complexes in situ, and demonstrates its power for addressing fundamental questions in cell biology. I will also briefly discuss the current challenges and future perspectives of the field of in situ cryo-ET.