Structural Biology in the Multi-Omics Era

Abstract

Rapid developments in cryogenic electron microscopy have opened new avenues to probe the structures of protein assemblies in their near native states. Recent studies have begun applying single -particle analysis to heterogeneous mixtures, revealing the potential of structural-omics approaches that combine the power of mass spectrometry and electron microscopy. Here we highlight advances and challenges in sample preparation, data processing, and molecular modeling for handling increasingly complex mixtures. Such advances will help structural-omics methods extend to cellular-level models of structural biology.

Figure 1

A structural-omics pipeline. A broad goal in the field is to develop a high-throughput structural-omics approach for reconstructing complexes from a heterogeneous mixture. For example, whole-cell lysates, organelle lysates, and heterogeneous mixtures might be analyzed by both cryo-EM and mass spectrometry. Cryo-EM produces multiple 3D reconstructions of protein complexes, while mass spectrometry provides identity and interaction information for the proteins present in the sample. To merge the two, even more efficient computational pipelines are needed to build or retrieve individual structures of proteins, organize them by interactions, assemble them into complexes, and match them to their 3D reconstructions obtained from a sample.