Anne-Claude Gavin is Group Leader in the Structural and Computational Biology Unit at the European Molecular Biology Laboratory, Heidelberg. Before joining the EMBL she was a scientific director at Cellzome AG. In 2002 she received the Genome Technology All-Stars Award in proteomics. Her group has been proponent and pioneer of more general strategies aiming at understanding complex biological systems. With more than 1’700 citations, the system-wide characterization of protein complexes in a model eukaryote, Saccharomyces cerevisiae, by affinity purification and mass spectrometry is generally considered as a breakthrough. Her main research interest includes the study of biomolecular interaction, the understanding of the principles that govern the assembly and dynamics of protein networks.

Abstract

Proteome Organization in a Genome-Reduced Bacterium

Biologists currently access exponentially growing lists of genomes from organisms covering all three domains of life. This has fundamentally changed the way scientists address biological questions. A spectacular flourishing of technologies allows for global interrogation of gene activity and function and ever more comprehensive measurement of cellular macromolecules. These OMICS approaches (genomics, proteomics, metabolomic) are still in full expansion, but already contribute extensive repertoires of the molecular constituents of a cell. However, biology does not rely on biomolecules acting in isolation. It rather depends on the concerted action of molecules acting in protein complexes, metabolic or signaling pathways or networks. Biomolecular interactions are central to all biological functions. In human, for example, impaired or deregulated protein–protein or protein–metabolite interaction often leads to disease. Recent strategies have been designed that allow the study of interactions more globally at the level of entire biological systems. We used tandem affinity purification–mass spectrometry (TAP-MS) in a proteome-wide screen for protein complexes in Mycoplasma pneumoniae, a human pathogen that causes atypical pneumonia. This self-replicating organism has one of the smallest known genomes (689 proteinencoding genes), making it an ideal model organism for the investigation of absolute essentiality. The analysis revealed 62 homomultimeric and 116 heteromultimeric soluble protein complexes, of which the majority are novel. About a third of the heteromultimeric complexes show higher levels of proteome organization, including assembly into larger, multiprotein complex entities, suggesting sequential steps in biological processes, and extensive sharing of components, implying protein multifunctionality. Incorporation of structural models for 484 proteins, single-particle electron microscopy, and cellular electron tomograms provided supporting structural details for this proteome organization. The data set provides a blueprint of the minimal cellular machinery required for life.