Insight into microtubule nucleation from tubulin-capping proteins.
Campanacci, V., Urvoas, A., Cantos-Fernandes, S., Aumont-Nicaise, M., Arteni, A.A., Velours, C., Valerio-Lepiniec, M., Dreier, B., Pluckthun, A., Pilon, A., Pous, C., Minard, P., Gigant, B.(2019) Proc Natl Acad Sci U S A 116: 9859-9864
- PubMed: 31036638 
- DOI: https://doi.org/10.1073/pnas.1813559116
- Primary Citation of Related Structures:  
6GVM, 6GVN, 6GX7 - PubMed Abstract: 
Nucleation is one of the least understood steps of microtubule dynamics. It is a kinetically unfavorable process that is templated in the cell by the ¦Ã-tubulin ring complex or by preexisting microtubules; it also occurs in vitro from pure tubulin. Here we study the nucleation inhibition potency of natural or artificial proteins in connection with their binding mode to the longitudinal surface of ¦Á- or ¦Â-tubulin. The structure of tubulin-bound CopN, a Chlamydia protein that delays nucleation, suggests that this protein may interfere with two protofilaments at the (+) end of a nucleus. Designed ankyrin repeat proteins that share a binding mode similar to that of CopN also impede nucleation, whereas those that target only one protofilament do not. In addition, an ¦ÁRep protein predicted to target two protofilaments at the (-) end does not delay nucleation, pointing to different behaviors at both ends of the nucleus. Our results link the interference with protofilaments at the (+) end and the inhibition of nucleation.
Organizational Affiliation: 
Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Universit¨¦ Paris-Sud, Universit¨¦ Paris-Saclay, 91198 Gif-sur-Yvette Cedex, France.