The Oligomeric Outer Dynein Arm Assembly Factor CCDC103 Is Tightly Integrated within the Ciliary Axoneme and Exhibits Periodic Binding to Microtubules

King, Stephen M.; Patel‐King, Ramila S.

doi:10.1074/jbc.m114.616425

Cited by 51 publications

(75 citation statements)

References 37 publications

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“…In the Chlamydomonas protein (CrCCDC103), we identify a C-terminal segment capable of independent dimerization which is consistent with the ability of CrCCDC103, but not HsCCDC103, to form stable tetramers in vitro (King & Patel-King, 2015). We find that dimerization is mediated through an inherently disordered region located between the N-terminal coiled coil and the RPAP3_C domain.…”

Section: Introductionsupporting

confidence: 70%

“…Much of this (16 residues) forms an extended Gly/Ala/Glu-rich loop within the RPAP3_C domain; intriguingly, this extension occurs immediately adjacent to the site of the human PCD-causing mutation H154P (King & Patel-King, 2015). Much of this (16 residues) forms an extended Gly/Ala/Glu-rich loop within the RPAP3_C domain; intriguingly, this extension occurs immediately adjacent to the site of the human PCD-causing mutation H154P (King & Patel-King, 2015).…”

Section: Domain Organization Of Ccdc103mentioning

confidence: 99%

“…CCDC103 exhibits unusual biophysical properties including the formation of dimers and higher order structures that are stable to, or reform after, heating in the presence of detergent (King & Patel-King, 2015;Panizzi et al, 2012). CCDC103 exhibits unusual biophysical properties including the formation of dimers and higher order structures that are stable to, or reform after, heating in the presence of detergent (King & Patel-King, 2015;Panizzi et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

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The outer dynein arm assembly factor CCDC103 forms molecular scaffolds through multiple self‐interaction sites

King

Patel‐King

2019

Cytoskeleton

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CCDC103 is a small protein with unusual biophysical properties that is required for outer dynein arm assembly on ciliary axonemes. Mutations in both human and zebrafish CCDC103 proteins lead to primary ciliary dyskinesia. Previous studies revealed that this protein can oligomerize and appears to be arrayed along the entire length of the ciliary axoneme. CCDC103 also binds purified microtubules directly and indeed stabilizes them. Here we use biochemical approaches to identify two regions of CCDC103 that mediate self-interaction. In both cases, these associations are stable to heating in the presence of detergent and are not disrupted by strong reducing agents. One interaction region consists of a 27-residue inherently disorder segment that can mediate heat/detergent-resistant dimerization when attached to unrelated monomeric proteins. The second interface includes the C-terminal RPAP3_C alpha helical domain. Our data suggest that CCDC103 can form an unconventional polymer and we propose models for how the monomers might be organized. We also use molecular modeling of the RPAP3_C domain to determine the structural consequences of the pathogenic H154P mutation found in human PCD patients. K E Y W O R D S Axoneme, Chlamydomonas, cilia, dynein, flagella, microtubule ABBREVIATIONS: CCDC, coiled coil domain containing; FAP, flagella-associated protein; MBP, maltose-binding protein; ODA-DC, outer dynein arm docking complex; RPAP3, RNA polymerase II-associated protein 3; TCEP, Tris(2-carboxyethyl)phosphine.

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Section: Introductionsupporting

confidence: 70%

Section: Domain Organization Of Ccdc103mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The outer dynein arm assembly factor CCDC103 forms molecular scaffolds through multiple self‐interaction sites

King

Patel‐King

2019

Cytoskeleton

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“…In order to determine whether any other axonemal proteins, such as CCDC103 (King and Patel-King, 2015;Panizzi et al, 2012), were required for the 24-nm periodicity of the ODA, we also incubated ODAs with cytoplasmic microtubules that had been purified from porcine brains. The ODAs regularly bound to the porcine microtubules with 24-nm periodicity in the presence and absence of docking complex ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Docking-complex-independent alignment of Chlamydomonas outer dynein arms with 24-nm periodicity in vitro

Oda

Abe

Yanagisawa

et al. 2016

Journal of Cell Science

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The docking complex is a molecular complex necessary for assembly of outer dynein arms (ODAs) on the axonemal doublet microtubules (DMTs) in cilia and flagella. The docking complex is hypothesized to be a 24-nm molecular ruler because ODAs align along the DMTs with 24-nm periodicity. In this study, we rigorously tested this hypothesis using structural and genetic methods. We found that the ODAs can bind to DMTs and porcine microtubules with 24-nm periodicities even in the absence of the docking complex in vitro. Using cryo-electron tomography and structural labeling, we observed that the docking complex took an unexpectedly flexible conformation and did not lie along the length of DMTs. In the absence of docking complex, ODAs were released from the DMT at relatively low ionic strength conditions, suggesting that the docking complex strengthens the electrostatic interactions between the ODA and DMT. Based on these results, we conclude that the docking complex serves as a flexible stabilizer of the ODA rather than as a molecular ruler.

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“…ARMC4 interacts with DNAI2 and is considered to be involved in the specific targeting and anchoring of OAD [160]. CCDC103 binds tightly to microtubules and appears to have a role in attachment of OAD [161,162]. C21orf59/ FBB18 is a flagellar matrix protein and participates in dynein arm assembly.…”

Section: Factors For Intraciliary Docking and Regulation Of Oadmentioning

confidence: 99%

Sperm dysfunction and ciliopathy

Inaba

Mizuno

2015

Reprod Medicine & Biology

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The Oligomeric Outer Dynein Arm Assembly Factor CCDC103 Is Tightly Integrated within the Ciliary Axoneme and Exhibits Periodic Binding to Microtubules

Cited by 51 publications

References 37 publications

The outer dynein arm assembly factor CCDC103 forms molecular scaffolds through multiple self‐interaction sites

The outer dynein arm assembly factor CCDC103 forms molecular scaffolds through multiple self‐interaction sites

Docking-complex-independent alignment of Chlamydomonas outer dynein arms with 24-nm periodicity in vitro

Sperm dysfunction and ciliopathy

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