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今日快三开奖结果广西:Insight into microtubule nucleation from tubulin-capping proteins
广东快乐十分投注下载 www.hmclip.net Edited by Antonina Roll-Mecak, National Institute of Neurological Disorders and Stroke, Bethesda, MD, and accepted by Editorial Board Member Sue Biggins April 5, 2019 (received for review August 7, 2018)
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Microtubules are involved in many key functions of eukaryotic cells, including cell division, intracellular transport, and cell shape. They are hollow tubes made of parallel filaments, themselves formed by the self-assembly of αβ-tubulin molecules. Whereas microtubules lengthen and shorten from their ends dynamically, their birth, called nucleation, remains poorly understood. To gain information on this process, we have determined the structure of tubulin bound to CopN, a bacterial protein that delays nucleation. Together with the behavior of artificial tubulin-binding proteins, our results lead to the hypothesis that targeting two filaments at the fast-growing end of the microtubule inhibits nucleation. They also suggest different dynamics at both ends of the nucleus.
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 γ-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 α- or β-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 αRep 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.
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Author contributions: V.C., C.P., P.M., and B.G. designed research; V.C., A.U., S.C.-F., M.A.-N., A.-A.A., C.V., A. Pilon, C.P., and B.G. performed research; B.D. and A. Plückthun contributed new reagents/analytic tools; V.C., A.U., M.V.-L., A. Pilon, C.P., P.M., and B.G. analyzed data; and C.P. and B.G. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission. A.R.-M. is a guest editor invited by the Editorial Board.
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1813559116/-/DCSupplemental.
Published under the PNAS license.