Tubulin and FtsZ Superfamily of Protein Assembly Machines

Abstract

Abstract Eukaryotic αβ‐tubulin and bacterial FtsZ self‐assemble into dynamic cytoskeletal polymers, microtubules or filaments, which are essential for chromosome segregation or bacterial cell division, respectively. Both share homologous core structures with guanosine‐5'‐triphosphate (GTP) ‐binding and GTPase‐activating domains joined by a central helix, and form similar protofilaments with 4 nm spaced subunits along them. During assembly, the GTPase‐activating domain of one subunit associates with the GTP binding domain of the preceding subunit, completing the active site. GTP hydrolysis triggers disassembly, which is coupled to free subunits switching into inactive conformation. Microtubule dynamics is inhibited by anticancer drugs binding near tubulin assembly interfaces. FtsZ is a target for new antibiotics discovery; several bacterial division inhibitors bind between FtsZ domains or at its GTP site. Other proteins in this superfamily include: gamma‐tubulin that is essential for microtubule organisation; bacterial tubulin, a primitive structural homologue; and recently discovered TubZ, distant homologue employed by plasmids and phages for deoxyribonucleic acid positioning. Key Concepts: Tubulin superfamily proteins share a common fold within two domains that is different from other GTPases. They assemble into microtubules and other different types of dynamic cytoskeletal filaments. GTP hydrolysis is activated upon assembly and triggers disassembly. Tubulin homologues spread among most organisms, where they are central to essential functions including DNA segregation or cell division. They have important biomedical implications. Several effective antitumor drugs work by impairing microtubule dynamics. FtsZ is a target for new antibiotics.