Year: 2025
Type: article
Abstract: How microtubules (MTs) are generated in the proper orientation is essential to understanding how the cytoskeleton organizes a cell and MT-dependent events such as cell division. In the spindle, most MTs are generated through the branching MT nucleation pathway. In this pathway, new MTs are nucleated from the side of existing MTs and oriented at a shallow angle by the branching factor augmin, ensuring that both MTs have the same polarity. Yet, how augmin binds MTs and sets the branch angle has remained unclear. Here, we report the cryo-electron microscopy structure of an augmin subcomplex on the MT. This structure resembles that of NDC80 bound to the MT, with the conserved CH domain of augmin’s Haus6 subunit directly proximal to the MT lattice. We find that the Haus6 CH domain is a bona fide MT binding site that increases augmin’s affinity for the MT and helps establish branch angle. A second binding site, located in the disordered N-terminus of Haus8, also establishes branch angle,. Thus, we find that augmin regulates MT branching using two domains, each tuned to modulate MT affinity and MT branch angle. This work expands our mechanistic understanding of branching MT nucleation and thus spindle formation. Here, authors report the structure of the augmin’s CH domain bound to the microtubule lattice and show that its Haus8 subunit binds tubulin tails. Both domains are critical for microtubule binding and for microtubules to branch at shallow angles.
Source: Nature Communications
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,990
Funders: National Science Foundation, U.S. Department of Health and Human Services, Helen Hay Whitney Foundation, Princeton Center for Complex Materials, National Institutes of Health, University of California, San Francisco, Materials Research Science and Engineering Center, Harvard University, National Institute of General Medical Sciences, Division of Materials Research
Awards: G1644031019, G1746067696, G1796337455, G1907146399, G2174132073, G2433208693, G2497455034, How to make a microtubule organizing center, G32252468, Resource for Biocomputing Visualization and Informatics, G340396948, G3603580073, G3835604489, G3923339477, G4617261419, G4815039349, G5462837166, G5528850602, G5724233021, Role and Mechanisms of Microtubule Nucleation in Spindle Assembly, G6475176268, G6536552022, Princeton Center for Complex Materials, G7361609772, Structure-based mechanism of the augmin complex in promoting branching microtubule nucleation and spindle assembly, Structural and functional studies of axonemal microtubule inner proteins (MIPs), G9000001160, G9000061601, G9000086851, G9000131913, How to make a microtubule organizing center
OpenAlex ID: W4415738269