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Mechanistic origins of dynamic instability in filaments from the phage tubulin, PhuZ

TitleMechanistic origins of dynamic instability in filaments from the phage tubulin, PhuZ
Publication TypeJournal Article
Year of Publication2018
AuthorsZehr, EA, Rohou A, Liu Y, Verba KA, Pogliano J, Grigorieff N, Agard DA
Refereed DesignationNon-Refereed
JournalbiorXiv
Date Published05/2018
Abstract

A bacteriophage-encoded tubulin homologue, PhuZ, harnesses dynamic instability to position genomes of ϕKZ-like bacteriophage at the midline of their Pseudomonas hosts, facilitating phage infectivity. While much has been learned about molecular origins of microtubule dynamics, how GTP binding and hydrolysis control dynamics in the divergent 3-stranded PhuZ filaments is not understood. Here we present cryo-EM reconstructions of the PhuZ filamentin a pre-hydrolysis (3.5Å) and three post-hydrolysis states (4.2 Å, 7.3 Å and 8.1 Å resolutions), likely representing distinct depolymerization stages. Core polymerization-induced structural changes reveal similarities to αβ-tubulin, suggesting broad conservation within the tubulin family. By contrast, GTP hydrolysis is sensed quite differently and is communicated by the divergent PhuZ C-terminus to the lateral interface, leading to PhuZ polymer destabilization. This provides a contrasting molecular description of how nucleotide state can be harnessed by the tubulin fold to regulate filament assembly, metastability and disassembly.

URLhttps://www.biorxiv.org/content/early/2018/04/30/311498
DOI10.1101/311498
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Zehr_2018.pdf18.46 MB