In summary, we provide the first structural model for CM1 autoinhibition, a key mechanism that helps spatially regulate #microtubule nucleation. We also highlight key evolutionary differences in CM1 binding mechanisms.
@pconduit.bsky.socialPaul Conduit
@pconduit.bsky.social
Biologist and sports fan
@pconduit.bsky.social@pconduit.bsky.socialCAI is absent from human proteins, where a conserved SCC-LCC CM1 hairpin that blocks one of the key F residues is sufficient for autoinhibition. In contrast, this hairpin is necessary for CM1 binding in Drosophila Cnn, explaining the requirement for CAI domain-mediated autoinhibition.
@pconduit.bsky.socialIn this latest paper, we show that the CAI domain forms a 4-helix dimer that associates with the short coiled-coil (SCC) part of the CM1 domain (equivalent of g-TuNA in humans), blocking the otherwise exposed key phenylalanine (F115) residue required for g-TuRC binding.
@pconduit.bsky.socialWe previously showed that an upstream CM1 autoinhibition domain is required to prevent binding and activation of g-TuRCs by #Drosophila Centrosomin (Cnn) to avoid ectopic cytosolic #microtubule nucleation and major #cell and #developmental defects
rupress.org/jcb/article/...
@pconduit.bsky.socialHappy to see our latest work published in @jcb.org. Led by an excellent PhD student, Abir Elfarkouchi, and in collaboration with @francoizochsenbein.bsky.social and co-first author Arthur Vitard, we investigated the structural mechanism of CM1 domain autoinhibition rupress.org/jcb/article/...
@jcb.orgReposted by @pconduit.bsky.socialAbir Elfarkouchi, Arthur Vitard, @francoizochsenbein.bsky.social, @pconduit.bsky.social et al. reveal the first structural model for γ-TuRC CM1 domain autoinhibition, which prevents ectopic binding and activation of #microtubule-nucleating γ-tubulin ring complexes. rupress.org/jcb/article/...
