Chlamydomonas FBB18 is a ubiquitin-like protein essential for the cytoplasmic preassembly of various ciliary dyneins

Yamamoto, Ryosuke; Sahashi, Yui; Shimo-Kon, Rieko; Sakato-Antoku, Miho; Suzuki, Miyuka; Luo, Leo; Tanaka, Hideaki; Ishikawa, Takashi; Yagi, Toshiki; King, Stephen M.; Kurisu, Genji; Kon, Takahide

doi:https://doi.org/10.1073/pnas.2423948122

Chlamydomonas FBB18 is a ubiquitin-like protein essential for the cytoplasmic preassembly of various ciliary dyneins

Yamamoto, Ryosuke; Sahashi, Yui; Shimo-Kon, Rieko et al.

Proceedings of the National Academy of Sciences of the United States of America, 2025, 122(12), e2423948122

Number of Access:1,043（2025-08-14 21:06 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/101069

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Title	Chlamydomonas FBB18 is a ubiquitin-like protein essential for the cytoplasmic preassembly of various ciliary dyneins
Creator	NRID 1000010743114 1000010743114 researchmap permalink chlamydomonas chlamydomonas Scopus Author ID 55198261600 55198261600 CreatorName Yamamoto, Ryosuke
	CreatorName Sahashi, Yui
	NRID 1000080392877 1000080392877 CreatorName Shimo-Kon, Rieko
	CreatorName Sakato-Antoku, Miho
	CreatorName Suzuki, Miyuka
	CreatorName Luo, Leo
	NRID 1000040346169 1000040346169 CreatorName Tanaka, Hideaki
	CreatorName Ishikawa, Takashi
	NRID 1000040292833 1000040292833 CreatorName Yagi, Toshiki
	CreatorName King, Stephen M.
	NRID 1000090294131 1000090294131 ORCID 0000-0002-5354-0807 0000-0002-5354-0807 researchmap permalink read0051718 read0051718 Scopus Author ID 6701675123 6701675123 CreatorName Kurisu, Genji
	NRID 1000030332620 1000030332620 ORCID 0000-0002-1231-7609 0000-0002-1231-7609 researchmap permalink read0067779 read0067779 Scopus Author ID 7005425389 7005425389 CreatorName Kon, Takahide
Subject	CFAP298 (DNAAF16/C21ORF59)
	cilia
	dynein
	FBB18 (DAB2)
	ubiquitin
Description	Yamamoto R., Sahashi Y., Shimo-Kon R., et al. Chlamydomonas FBB18 is a ubiquitin-like protein essential for the cytoplasmic preassembly of various ciliary dyneins. Proceedings of the National Academy of Sciences of the United States of America 122, e2423948122 (2025); https://doi.org/10.1073/pnas.2423948122.
Abstract	Motile cilia are organelles found on many eukaryotic cells that play critical roles in development and fertility. Human CFAP298 has been implicated in the transport/assembly of ciliary dyneins, and defects in this protein cause primary ciliary dyskinesia. However, neither the exact function nor the structure of CFAP298 have been elucidated. Here, we took advantage of Chlamydomonas, a ciliated alga, to study the structure and function of FBB18, an ortholog of CFAP298. Multiple ciliary dyneins were greatly reduced in cilia of Chlamydomonas fbb18 mutants. In addition, we found that both the stability of ciliary dynein heavy chains (HCs) and the association between HCs and intermediate/light chains (IC/LCs) are greatly reduced in fbb18 cytoplasm, strongly suggesting that FBB18 functions in the cytoplasmic assembly (the so-called “preassembly”) of dynein complexes from HC/IC/LCs. Furthermore, X-ray crystallography revealed that FBB18 forms a bilobed structure with globular domains at both ends of the molecule, connected by an α-helical bundle. Unexpectedly, one globular domain shows high similarity to ubiquitin, a small protein critical for the modification of a variety of protein complexes, and this ubiquitin-like domain is indispensable for the molecular function of FBB18. Our results demonstrate that FBB18, a specialized member of the ubiquitin-like protein family, plays a critical role in dynein preassembly, most likely by mediating diverse interactions between dynein HCs, molecular chaperone(s), and other preassembly factor(s) using the ubiquitin-like domain as well as other regions, and by facilitating the proper folding of dynein HCs.
Publisher	National Academy of Sciences
Source Title	Proceedings of the National Academy of Sciences of the United States of America
Volume (Issue)	122(12)
Page	e2423948122
Date of Issued	2025-03-19
Language	English
Handle URL	https://hdl.handle.net/11094/101069
PISSN	00278424
eISSN	10916490
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.1073/pnas.2423948122
Access Rights	embargoed access
CopyRight	The full-text file will be made open to the public under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) on 19 September 2025 in accordance with the publisher's policy.
CopyRight	This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
oaire:version	Version of Record
Category	学術雑誌論文 Journal Article

Resource Type	journal article
Local Type	Journal Article
DCMI Type	Text
DCTERMS.bibliographicCitation	Proceedings of the National Academy of Sciences of the United States of America. 2025, 122(12), p. e2423948122
DC.title	Chlamydomonas FBB18 is a ubiquitin-like protein essential for the cytoplasmic preassembly of various ciliary dyneins
DC.creator	Yamamoto, Ryosuke
	Sahashi, Yui
	Shimo-Kon, Rieko
	Sakato-Antoku, Miho
	Suzuki, Miyuka
	Luo, Leo
	Tanaka, Hideaki
	Ishikawa, Takashi
	Yagi, Toshiki
	King, Stephen M.
	Kurisu, Genji
	Kon, Takahide
DC.publisher	National Academy of Sciences
DC.language' scheme='DCTERMS.RFC1766	English
DC.type' scheme='DCTERMS.DCMIType	Text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2025-03-19
DC.identifier	https://doi.org/10.1073/pnas.2423948122
DC.subject	CFAP298 (DNAAF16/C21ORF59)
	cilia
	dynein
	FBB18 (DAB2)
	ubiquitin
DC.description	Yamamoto R., Sahashi Y., Shimo-Kon R., et al. Chlamydomonas FBB18 is a ubiquitin-like protein essential for the cytoplasmic preassembly of various ciliary dyneins. Proceedings of the National Academy of Sciences of the United States of America 122, e2423948122 (2025); https://doi.org/10.1073/pnas.2423948122.
DCTERMS.abstract	Motile cilia are organelles found on many eukaryotic cells that play critical roles in development and fertility. Human CFAP298 has been implicated in the transport/assembly of ciliary dyneins, and defects in this protein cause primary ciliary dyskinesia. However, neither the exact function nor the structure of CFAP298 have been elucidated. Here, we took advantage of Chlamydomonas, a ciliated alga, to study the structure and function of FBB18, an ortholog of CFAP298. Multiple ciliary dyneins were greatly reduced in cilia of Chlamydomonas fbb18 mutants. In addition, we found that both the stability of ciliary dynein heavy chains (HCs) and the association between HCs and intermediate/light chains (IC/LCs) are greatly reduced in fbb18 cytoplasm, strongly suggesting that FBB18 functions in the cytoplasmic assembly (the so-called “preassembly”) of dynein complexes from HC/IC/LCs. Furthermore, X-ray crystallography revealed that FBB18 forms a bilobed structure with globular domains at both ends of the molecule, connected by an α-helical bundle. Unexpectedly, one globular domain shows high similarity to ubiquitin, a small protein critical for the modification of a variety of protein complexes, and this ubiquitin-like domain is indispensable for the molecular function of FBB18. Our results demonstrate that FBB18, a specialized member of the ubiquitin-like protein family, plays a critical role in dynein preassembly, most likely by mediating diverse interactions between dynein HCs, molecular chaperone(s), and other preassembly factor(s) using the ubiquitin-like domain as well as other regions, and by facilitating the proper folding of dynein HCs.
DC.rights	The full-text file will be made open to the public under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) on 19 September 2025 in accordance with the publisher's policy.
DC.rights	This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
DC.format	101069
citation_title	Chlamydomonas FBB18 is a ubiquitin-like protein essential for the cytoplasmic preassembly of various ciliary dyneins
citation_author	Yamamoto, Ryosuke
	Sahashi, Yui
	Shimo-Kon, Rieko
	Sakato-Antoku, Miho
	Suzuki, Miyuka
	Luo, Leo
	Tanaka, Hideaki
	Ishikawa, Takashi
	Yagi, Toshiki
	King, Stephen M.
	Kurisu, Genji
	Kon, Takahide
citation_publisher	National Academy of Sciences
citation_language	English
citation_date	2025-03-19
citation_journal_title	Proceedings of the National Academy of Sciences of the United States of America
citation_volume	122
citation_issue	12
citation_firstpage	e2423948122
citation_doi	https://doi.org/10.1073/pnas.2423948122
citation_public_url	https://hdl.handle.net/11094/101069

Chlamydomonas FBB18 is a ubiquitin-like protein essential for the cytoplasmic preassembly of various ciliary dyneins

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