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The HAUS6 CH domain binds microtubules to orient augmin for microtubule branching

ABSTRACT: Branching microtubule nucleation is a key mechanism for mitotic and meiotic spindle assembly and requires the hetero-octameric augmin complex. Augmin recruits the major microtubule nucleator, the γ-tubulin ring complex, to pre-existing microtubules to direct the formation of new microtubules in a defined orientation. Although recent structural work has provided key insights into augmin’s structural organization, molecular details of its interaction with microtubules remain elusive. Here, we identify the minimal conserved microtubule-binding unit of augmin across species and demonstrate that the low-complexity microtubule-binding unit from D. melanogaster mediates microtubule binding predominantly via the calponin homology (CH) domain in Dgt6/HAUS6. Comparative sequence and functional analyses reveal a highly conserved architecture of the HAUS6 CH domain and variations in the importance of the HAUS8 N-terminus in microtubule binding. Using cryo-electron microscopy and molecular dynamics simulations, we show that the HAUS6 CH domain binds at the inter-protofilament groove between two adjacent β-tubulin subunits and thereby orients augmin on microtubules. Altogether, our findings reveal how augmin binds microtubules to pre-determine the branching angle during microtubule nucleation and thereby facilitates the rapid assembly of complex microtubule networks.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human) Escherichia Coli Xenopus Laevis (african Clawed Frog) Arabidopsis Thaliana (mouse-ear Cress) Drosophila Melanogaster (fruit Fly)

SUBMITTER: Marcin Luzarowski