KAUST Research Conference

Computational Advances in Structural Biology

May 1 - 3, 2023 Auditorium between building 4 & 5

Determining structures of membrane proteins by cryo-ET


Abstract :

Subtomogram averaging from cryo electron tomograms is a powerful method to determine structures of macromolecules in their native state. Outstanding applications to protein lattices, coats and ribosomes provided unique insights into their functions and even revealed interactions with small molecules in situ. For other macromolecules, such as membrane proteins, which are present in tomograms in limited numbers, the throughput of data processing and the processing time are key bottlenecks in obtaining high-resolution reconstructions. This is particularly the case for membrane proteins that are typically present in tomograms in moderate amounts.

I will introduce the tools that we developed in our lab for in situ structural biology with a focus on a large ion channel RyR1 which is a part of the excitation-contraction coupling in muscle. TomoBEAR is a workflow for processing of tomographic data utilizing common cryo-EM tools and original code that allows transparent near-automated tomographic pre-processing, alignment, reconstruction and particle identification. Our substack-based analysis using SUSAN implemented for high performance computing allows up to several orders of magnitude speedup and produces high-resolution maps.

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