Gui, Miao;
Croft, Jacob T;
Zabeo, Davide;
Acharya, Vajradhar;
Kollman, Justin M;
Burgoyne, Thomas;
Höög, Johanna L;
(2022)
SPACA9 is a lumenal protein of human ciliary singlet and doublet microtubules.
Proceedings of the National Academy of Sciences
, 119
(41)
, Article e2207605119. 10.1073/pnas.2207605119.
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Abstract
The cilium-centrosome complex contains triplet, doublet, and singlet microtubules. The lumenal surfaces of each microtubule within this diverse array are decorated by microtubule inner proteins (MIPs). Here, we used single-particle cryo-electron microscopy methods to build atomic models of two types of human ciliary microtubule: the doublet microtubules of multiciliated respiratory cells and the distal singlet microtubules of monoflagellated human spermatozoa. We discover that SPACA9 is a polyspecific MIP capable of binding both microtubule types. SPACA9 forms intralumenal striations in the B tubule of respiratory doublet microtubules and noncontinuous spirals in sperm singlet microtubules. By acquiring new and reanalyzing previous cryo-electron tomography data, we show that SPACA9-like intralumenal striations are common features of different microtubule types in animal cilia. Our structures provide detailed references to help rationalize ciliopathy-causing mutations and position cryo-EM as a tool for the analysis of samples obtained directly from ciliopathy patients.
Type: | Article |
---|---|
Title: | SPACA9 is a lumenal protein of human ciliary singlet and doublet microtubules |
Open access status: | An open access version is available from UCL Discovery |
DOI: | 10.1073/pnas.2207605119 |
Publisher version: | https://doi.org/10.1073/pnas.2207605119 |
Language: | English |
Additional information: | Copyright © 2022 the Author(s). Published by PNAS. This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY). |
UCL classification: | UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL |
URI: | https://discovery.ucl.ac.uk/id/eprint/10156726 |
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