RRC ID 60764
Author Huang TL, Wang HJ, Chang YC, Wang SW, Hsia KC.
Title Promiscuous Binding of Microprotein Mozart1 to γ-Tubulin Complex Mediates Specific Subcellular Targeting to Control Microtubule Array Formation.
Journal Cell Rep
Abstract How γ-tubulin ring complex (γ-TuRC), a master template for microtubule nucleation, is spatially and temporally regulated for the assembly of new microtubule arrays remains unclear. Here, we report that an evolutionarily conserved microprotein, Mozart1 (Mzt1), regulates subcellular targeting and microtubule formation activity of γ-TuRC at different cell cycle stages. Crystal structures of protein complexes demonstrate that Mzt1 promiscuously interacts with the N-terminal domains of multiple γ-tubulin complex protein subunits in γ-TuRC via an intercalative binding mode. Genetic- and microscopy-based analyses show that promiscuous binding of Mzt1 in γ-TuRC controls specific subcellular localization of γ-TuRC to modulate microtubule nucleation and stabilization in fission yeast. Moreover, we find Mzt1-independent targeting of γ-TuRC to be crucial for mitotic spindle assembly, demonstrating the cell-cycle-dependent regulation and function of γ-TuRC. Our findings reveal a microprotein-mediated regulatory mechanism underlying microtubule cytoskeleton formation, whereby Mzt1 binding promiscuity confers localization specificity on the multi-protein complex γ-TuRC.
Volume 31(13)
Pages 107836
Published 2020-6-30
DOI 10.1016/j.celrep.2020.107836
PII S2211-1247(20)30817-2
PMID 32610137
MeSH Conserved Sequence Evolution, Molecular* Humans Interphase Microtubule-Associated Proteins / chemistry Microtubule-Associated Proteins / metabolism* Microtubule-Organizing Center / metabolism Microtubules / metabolism* Mitosis Models, Biological Multiprotein Complexes / metabolism* Protein Binding Protein Domains Schizosaccharomyces / growth & development Schizosaccharomyces / metabolism* Schizosaccharomyces pombe Proteins / chemistry Schizosaccharomyces pombe Proteins / metabolism* Sequence Deletion Solutions Spindle Pole Bodies / metabolism Subcellular Fractions / metabolism Tubulin / metabolism*
IF 8.109
Times Cited 1
Yeast FY33776 (HR2379)