De novo identification of mammalian ciliary motility proteins using cryo-EM
File(s)1-s2.0-S0092867421011818-main.pdf (10.31 MB)
Published version
Author(s)
Type
Journal Article
Abstract
Dynein-decorated doublet microtubules (DMTs) are critical components of the oscillatory molecular machine of cilia, the axoneme, and have luminal surfaces patterned periodically by microtubule inner proteins (MIPs). Here we present an atomic model of the 48-nm repeat of a mammalian DMT, derived from a cryoelectron microscopy (cryo-EM) map of the complex isolated from bovine respiratory cilia. The structure uncovers principles of doublet microtubule organization and features specific to vertebrate cilia, including previously unknown MIPs, a luminal bundle of tektin filaments, and a pentameric dynein-docking complex. We identify a mechanism for bridging 48- to 24-nm periodicity across the microtubule wall and show that loss of the proteins involved causes defective ciliary motility and laterality abnormalities in zebrafish and mice. Our structure identifies candidate genes for diagnosis of ciliopathies and provides a framework to understand their functions in driving ciliary motility.
Date Issued
2021-11-11
Online Publication Date
2022-01-17T12:20:22Z
Date Acceptance
2021-10-07
ISSN
0092-8674
Publisher
CELL PRESS
Start Page
5791
End Page
5806.e19
Journal / Book Title
Cell
Volume
184
Issue
23
Copyright Statement
© 2021 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
License URI
Identifier
https://www.sciencedirect.com/science/article/pii/S0092867421011818?via%3Dihub
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000719154700002&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
Cell Biology
ARM-DOCKING COMPLEX
LEFT-RIGHT ASYMMETRY
OUTER ARM
SITUS-INVERSUS
DOUBLET MICROTUBULES
COILED-COIL
TEKTIN 3
DYNEIN
MUTATIONS
GENE
axonemal dyneins
ciliary motility
ciliopathies
cryo-EM
doublet microtubules
microtubule inner proteins
Amino Acid Sequence
Animals
Cattle
Cilia
Cryoelectron Microscopy
Dyneins
Embryo, Mammalian
Female
Male
Mammals
Mice, Inbred C57BL
Microtubule Proteins
Microtubules
Models, Molecular
Mutation
Proteins
Trachea
Zebrafish
Zebrafish Proteins
Trachea
Cilia
Microtubules
Animals
Mice, Inbred C57BL
Zebrafish
Mammals
Cattle
Microtubule Proteins
Proteins
Zebrafish Proteins
Cryoelectron Microscopy
Amino Acid Sequence
Mutation
Models, Molecular
Female
Male
Embryo, Mammalian
Dyneins
Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
Cell Biology
ARM-DOCKING COMPLEX
LEFT-RIGHT ASYMMETRY
OUTER ARM
SITUS-INVERSUS
DOUBLET MICROTUBULES
COILED-COIL
TEKTIN 3
DYNEIN
MUTATIONS
GENE
06 Biological Sciences
11 Medical and Health Sciences
Developmental Biology
Publication Status
Published
Date Publish Online
2021-10-28