RT Journal Article
A1 Muñoz-Hernández, Hugo
A1 Xu, Yixin
A1 Pellicer Camardiel, Aitor
A1 Zhang, Daniel
A1 Xue, Allen
A1 Aher, Amol
A1 Walker, Ellie
A1 Marxer, Florina
A1 Kapoor, Tarun M.
A1 Wieczorek, Michal
T1 Structure of the microtubule-anchoring factor NEDD1 bound to the γ-tubulin ring complex
JF Journal of Cell Biology
JO J Cell Biol
YR 2025
DO 10.1083/jcb.202410206
OP e202410206
VO 224
IS 8
SN 0021-9525
AB The γ-tubulin ring complex (γ-TuRC) is an essential multiprotein assembly that provides a template for microtubule nucleation. The γ-TuRC is recruited to microtubule-organizing centers (MTOCs) by the evolutionarily conserved attachment factor NEDD1. However, the structural basis of the NEDD1–γ-TuRC interaction is not known. Here, we report cryo-EM structures of NEDD1 bound to the human γ-TuRC in the absence or presence of the activating factor CDK5RAP2. We found that the C-terminus of NEDD1 forms a tetrameric α-helical assembly that contacts the lumen of the γ-TuRC cone and orients its microtubule-binding domain away from the complex. The structure of the γ-TuRC simultaneously bound to NEDD1 and CDK5RAP2 reveals that both factors can associate with the “open” conformation of the complex. Our results show that NEDD1 does not induce substantial conformational changes in the γ-TuRC but suggest that anchoring of γ-TuRC–capped microtubules by NEDD1 would be structurally compatible with the significant conformational changes experienced by the γ-TuRC during microtubule nucleation.
RD 5/24/2025
UL https://doi.org/10.1083/jcb.202410206