Molecular architecture of the augmin complex

• Published in: Nature communications Vol. 13; no. 1; p. 5449
• Main Authors: Gabel, Clinton A., Li, Zhuang, DeMarco, Andrew G., Zhang, Ziguo, Yang, Jing, Hall, Mark C., Barford, David, Chang, Leifu
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 16.09.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 101/28; 13; 631/45/612/1228; 631/535/1258/1259; 631/80/128/1653; 631/80/641/1656; 82/29; 82/58; 82/80; 82/83; Cell division; Chromosomes; Computer applications; Crosslinking; Cryoelectron Microscopy; Electron microscopy; Flexible structures; Homology; Humanities and Social Sciences; Mass spectrometry; Mass spectroscopy; Microtubule-Associated Proteins - metabolism; Microtubules; Microtubules - metabolism; Mitosis; Molecular structure; multidisciplinary; Nucleation; Protein structure; Proteins; Robustness; Science; Science (multidisciplinary); Scientific imaging; Software; Spectroscopy; Spindle Apparatus - metabolism; Spindles; Structural models; Tubulin; Tubulin - metabolism
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-33227-7

Accurate segregation of chromosomes during mitosis depends on the correct assembly of the mitotic spindle, a bipolar structure composed mainly of microtubules. The augmin complex, or homologous to augmin subunits (HAUS) complex, is an eight-subunit protein complex required for building robust mitotic spindles in metazoa. Augmin increases microtubule density within the spindle by recruiting the γ-tubulin ring complex (γ-TuRC) to pre-existing microtubules and nucleating branching microtubules. Here, we elucidate the molecular architecture of augmin by single particle cryo-electron microscopy (cryo-EM), computational methods, and crosslinking mass spectrometry (CLMS). Augmin’s highly flexible structure contains a V-shaped head and a filamentous tail, with the head existing in either extended or contracted conformational states. Our work highlights how cryo-EM, complemented by computational advances and CLMS, can elucidate the structure of a challenging protein complex and provides insights into the function of augmin in mediating microtubule branching nucleation. The eight-subunit augmin complex is required to nucleate branching microtubules and create a robust mitotic spindle during cell division. Here, the authors use cryo-EM, crosslinking mass spectrometry, and computational tools to build a structural model of the human augmin complex.