“Structural Studies of Biomolecular and Supramolecular Complexes”
_
Date and Time
4:00 PM – Friday, August 22, 2025
Location
KEK CryoEM building
Speakers: Ilkin Yapici
Koc University
Abstract
High-resolution structural studies continue to drive progress in both antibiotic development and neurodegenerative disease research. Building on our previous work using serial femtosecond X-ray crystallography (SFX) at XFELs to resolve 30S and 50S ribosomal subunits at ambient temperature, we are now extending our structural investigations to intact 70S ribosomes using single-particle cryo-electron microscopy. These cryo-EM studies aim to elucidate how next-generation antibiotics interact with the bacterial translation machinery, offering new insights into drug binding, resistance mechanisms, and ribosome functional dynamics under near-native conditions.
In parallel, we are investigating the structural features of ALS-linked superoxide dismutase 1 (SOD1) aggregates, with a focus on the H71Y mutant identified in Turkish patients. Cryo-EM and cryo-electron tomography (cryo-ET) reveal that this variant forms long, unbranched amyloid-like fibers with a characteristic hollow-core morphology and accelerated aggregation kinetics. Guided by these structural insights, we are screening a panel of hybrid small molecules incorporating radical-scavenging, metal-chelating, and ferroptosis-inhibiting elements. Preliminary data suggest these compounds may interfere with fiber growth, destabilize preformed filaments, or inhibit pathological seeding.
Together, these efforts illustrate how complementary high-resolution techniques, XFEL-based SFX and cryo-EM, can be leveraged to investigate both essential biomolecular complexes and disease-relevant protein assemblies. Our findings contribute to structure-guided strategies for the development of new antibiotics and therapeutic approaches for ALS.