Transition of human γ-tubulin ring complex into a closed conformation during microtubule nucleation

• 成果类型: Article
• 署名作者: Brito, Claudia; Serna, Marina; Guerra, Pablo; Llorca, Oscar; Surrey, Thomas
• 署名单位: Barcelona Institute of Science & Technology; Pompeu Fabra University; Centre de Regulacio Genomica (CRG); Centro Nacional de Investigaciones Oncologicas (CNIO); Pompeu Fabra University; ICREA
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-11225
• DOI: 10.1126/science.adk6160
• 发表日期: 2024-02-23
• 页码: 870-876
• 关键词: cryo-em; saccharomyces-cerevisiae; surface lattice; architecture; centrosome; refinement; interacts; template; SYSTEM; spc97p

摘要

Microtubules are essential for intracellular organization and chromosome segregation. They are nucleated by the gamma-tubulin ring complex (gamma TuRC). However, isolated vertebrate gamma TuRC adopts an open conformation that deviates from the microtubule structure, raising the question of the nucleation mechanism. In this study, we determined cryo-electron microscopy structures of human gamma TuRC bound to a nascent microtubule. Structural changes of the complex into a closed conformation ensure that gamma TuRC templates the 13-protofilament microtubules that exist in human cells. Closure is mediated by a latch that interacts with incorporating tubulin, making it part of the closing mechanism. Further rearrangements involve all gamma TuRC subunits and the removal of the actin-containing luminal bridge. Our proposed mechanism of microtubule nucleation by human gamma TuRC relies on large-scale structural changes that are likely the target of regulation in cells.