Ciliary central apparatus structure reveals mechanisms of microtubule patterning
— Research Profiles at Washington University School of Medicine Skip to main navigation Skip to search Skip to main content Research Profiles at Washington University School of Medicine Home Help & FAQ Home Profiles Departments, Divisions and Centers Research output Search by expertise, name or affiliation Ciliary central apparatus structure reveals mechanisms of microtubule patterning Miao Gui, Xiangli Wang, Susan K. Dutcher, Alan Brown, Rui Zhang Department of Genetics Division of Biology and Biomedical Sciences Institute of Clinical and Translational Sciences Department of Biochemistry & Molecular Biophysics Research output: Contribution to journal › Article › peer-review 1 Scopus citations Overview Fingerprint Abstract A pair of extensively modified microtubules form the central apparatus (CA) of the axoneme of most motile cilia, where they regulate ciliary motility. The external surfaces of both CA microtubules are patterned asymmetrically with large protein complexes that repeat every 16 or 32 nm. The composition of these projections and the mechanisms that establish asymmetry and longitudinal periodicity are unknown. Here, by determining cryo-EM structures of the CA microtubules, we identify 48 different CA-associated proteins, which in turn reveal mechanisms for asymmetric and periodic protein binding to microtubules. We identify arc-MIPs, a novel class of microtubule inner protein, that bind laterally across protofilaments and remodel tubulin structure and lattice contacts. The binding mechanisms utilized by CA proteins may be generalizable to other microtubule-associated proteins. These structures establish a foundation to elucidate the contributions of individual CA proteins to ciliary motility and ciliopathies. Original language English Pages (from-to) 483-492 Number of pages 10 Journal Nature Structural and Molecular Biology Volume 29 Issue number 5 DOIs https://doi.org/10.1038/s41594-022-00770-2 State Published - May 2022 Access to Document 10.1038/s41594-022-00770-2 Other files and links Link to publication in Scopus Fingerprint Dive into the research topics of 'Ciliary central apparatus structure reveals mechanisms of microtubule patterning'. Together they form a unique fingerprint. Microtubules Medicine & Life Sciences 100% Ciliopathies Medicine & Life Sciences 38% Axoneme Medicine & Life Sciences 37% Proteins Medicine & Life Sciences 37% Microtubule Proteins Medicine & Life Sciences 35% Microtubule-Associated Proteins Medicine & Life Sciences 30% Cilia Medicine & Life Sciences 29% Periodicity Medicine & Life Sciences 28% View full fingerprint Cite this APA Author BIBTEX Harvard Standard RIS Vancouver Gui, M., Wang, X., Dutcher, S. K., Brown, A., & Zhang, R. (2022). Ciliary central apparatus structure reveals mechanisms of microtubule patterning. Nature Structural and Molecular Biology, 29(5), 483-492. https://doi.org/10.1038/s41594-022-00770-2 Gui, Miao ; Wang, Xiangli ; Dutcher, Susan K. ; Brown, Alan ; Zhang, Rui. / Ciliary central apparatus structure reveals mechanisms of microtubule patterning. In: Nature Structural and Molecular Biology. 2022 ; Vol. 29, No. 5. pp. 483-492. @article{ae97be31261d4f3daa9fdaa116512ca5, title = "Ciliary central apparatus structure reveals mechanisms of microtubule patterning", abstract = "A pair of extensively modified microtubules form the central apparatus (CA) of the axoneme of most motile cilia, where they regulate ciliary motility. The external surfaces of both CA microtubules are patterned asymmetrically with large protein complexes that repeat every 16 or 32 nm. The composition of these projections and the mechanisms that establish asymmetry and longitudinal periodicity are unknown. Here, by determining cryo-EM structures of the CA microtubules, we identify 48 different CA-associated proteins, which in turn reveal mechanisms for asymmetric and periodic protein binding to microtubules. We identify arc-MIPs, a novel class of microtubule inner protein, that bind laterally across protofilaments and remodel tubulin structure and lattice contacts. The binding mechanisms utilized by CA proteins may be generalizable to other microtubule-associated proteins. These structures establish a foundation to elucidate the contributions of individual CA proteins to ciliary motility and ciliopathies.", author = "Miao Gui and Xiangli Wang and Dutcher, {Susan K.} and Alan Brown and Rui Zhang", note = "Funding Information: Cryo-EM data were collected at the Washington University in St. Louis Center for Cellular Imaging (WUCCI) and Case Western Research University (CWRU). We thank M. Rau and J. Fitzpatrick at WUCCI and W. Huang and K. Li at CWRU for microscopy support, J. Anderson for help with domain recognition and M. Bao for comments. M.G. is supported by a Charles A. King Trust Postdoctoral Research Fellowship. S.K.D. is supported by NIGMS grant R35GM131909 and R01HL128370. A.B. is supported by NIGMS grant 1R01GM141109, the Smith Family Foundation and the Pew Charitable Trusts. R.Z. is supported by NIGMS grant 1R01GM138854. Funding Information: Cryo-EM data were collected at the Washington University in St. Louis Center for Cellular Imaging (WUCCI) and Case Western Research University (CWRU). We thank M. Rau and J. Fitzpatrick at WUCCI and W. Huang and K. Li at CWRU for microscopy support, J. Anderson for help with domain recognition and M. Bao for comments. M.G. is supported by a Charles A. King Trust Postdoctoral Research Fellowship. S.K.D. is supported by NIGMS grant R35GM131909 and R01HL128370. A.B. is supported by NIGMS grant 1R01GM141109, the Smith Family Foundation and the Pew Charitable Trusts. R.Z. is supported by NIGMS grant 1R01GM138854. Publisher Copyright: {\textcopyright} 2022, The Author(s), under exclusive licence to Springer Nature America, Inc.", year = "2022", month = may, doi = "10.1038/s41594-022-00770-2", language = "English", volume = "29", pages = "483--492", journal = "Nature Structural and Molecular Biology", issn = "1545-9993", number = "5", } Gui, M, Wang, X, Dutcher, SK, Brown, A & Zhang, R 2022, 'Ciliary central apparatus structure reveals mechanisms of microtubule patterning', Nature Structural and Molecular Biology, vol. 29, no. 5, pp. 483-492. https://doi.org/10.1038/s41594-022-00770-2 Ciliary central apparatus structure reveals mechanisms of microtubule patterning. / Gui, Miao; Wang, Xiangli; Dutcher, Susan K.; Brown, Alan; Zhang, Rui. In: Nature Structural and Molecular Biology, Vol. 29, No. 5, 05.2022, p. 483-492. Research output: Contribution to journal › Article › peer-review TY - JOUR T1 - Ciliary central apparatus structure reveals mechanisms of microtubule patterning AU - Gui, Miao AU - Wang, Xiangli AU - Dutcher, Susan K. AU - Brown, Alan AU - Zhang, Rui N1 - Funding Information: Cryo-EM data were collected at the Washington University in St. Louis Center for Cellular Imaging (WUCCI) and Case Western Research University (CWRU). We thank M. Rau and J. Fitzpatrick at WUCCI and W. Huang and K. Li at CWRU for microscopy support, J. Anderson for help with domain recognition and M. Bao for comments. M.G. is supported by a Charles A. King Trust Postdoctoral Research Fellowship. S.K.D. is supported by NIGMS grant R35GM131909 and R01HL128370. A.B. is supported by NIGMS grant 1R01GM141109, the Smith Family Foundation and the Pew Charitable Trusts. R.Z. is supported by NIGMS grant 1R01GM138854. Funding Information: Cryo-EM data were collected at the Washington University in St. Louis Center for Cellular Imaging (WUCCI) and Case Western Research University (CWRU). We thank M. Rau and J. Fitzpatrick at WUCCI and W. Huang and K. Li at CWRU for microscopy support, J. Anderson for help with domain recognition and M. Bao for comments. M.G. is supported by a Charles A. King Trust Postdoctoral Research Fellowship. S.K.D. is supported by NIGMS grant R35GM131909 and R01HL128370. A.B. is supported by NIGMS grant 1R01GM141109, the Smith Family Foundation and the Pew Charitable Trusts. R.Z. is supported by NIGMS grant 1R01GM138854. Publisher Copyright: © 2022, The Author(s), under exclusive licence to Springer Nature America, Inc. PY - 2022/5 Y1 - 2022/5 N2 - A pair of extensively modified microtubules form the central apparatus (CA) of the axoneme of most motile cilia, where they regulate ciliary motility. The external surfaces of both CA microtubules are patterned asymmetrically with large protein complexes that repeat every 16 or 32 nm. The composition of these projections and the mechanisms that establish asymmetry and longitudinal periodicity are unknown. Here, by determining cryo-EM structures of the CA microtubules, we identify 48 different CA-associated proteins, which in turn reveal mechanisms for asymmetric and periodic protein binding to microtubules. We identify arc-MIPs, a novel class of microtubule inner protein, that bind laterally across protofilaments and remodel tubulin structure and lattice contacts. The binding mechanisms utilized by CA proteins may be generalizable to other microtubule-associated proteins. These structures establish a foundation to elucidate the contributions of individual CA proteins to ciliary motility and ciliopathies. AB - A pair of extensively modified microtubules form the central apparatus (CA) of the axoneme of most motile cilia, where they regulate ciliary motility. The external surfaces of both CA microtubules are patterned asymmetrically with large protein complexes that repeat every 16 or 32 nm. The composition of these projections and the mechanisms that establish asymmetry and longitudinal periodicity are unknown. Here, by determining cryo-EM structures of the CA microtubules, we identify 48 different CA-associated proteins, which in turn reveal mechanisms for asymmetric and periodic protein binding to microtubules. We identify arc-MIPs, a novel class of microtubule inner protein, that bind laterally across protofilaments and remodel tubulin structure and lattice contacts. The binding mechanisms utilized by CA proteins may be generalizable to other microtubule-associated proteins. These structures establish a foundation to elucidate the contributions of individual CA proteins to ciliary motility and ciliopathies. UR - http://www.scopus.com/inward/record.url?scp=85130208066&partnerID=8YFLogxK U2 - 10.1038/s41594-022-00770-2 DO - 10.1038/s41594-022-00770-2 M3 - Article C2 - 35578023 AN - SCOPUS:85130208066 VL - 29 SP - 483 EP - 492 JO - Nature Structural and Molecular Biology JF - Nature Structural and Molecular Biology SN - 1545-9993 IS - 5 ER - Gui M, Wang X, Dutcher SK, Brown A, Zhang R. Ciliary central apparatus structure reveals mechanisms of microtubule patterning. Nature Structural and Molecular Biology. 2022 May;29(5):483-492. https://doi.org/10.1038/s41594-022-00770-2 Powered by Pure, Scopus & Elsevier Fingerprint Engine™ © 2022 Elsevier B.V We use cookies to help provide and enhance our service and tailor content. By continuing you agree to the use of cookies About web accessibility
