The RPAP3-Cterminal domain identifies R2TP-like quaternary chaperones

Maurizy, Chloé; Quinternet, Marc; Abel, Yoann; Verheggen, Céline; Santo, Paulo E.; Bourguet, Maxime; Paiva, Ana C. F.; Bragantini, Benoît; Chagot, Marie-Eve; Robert, Marie-Cécile; Abéza, Claire; Fabre, Philippe; Fort, Philippe; Vandermoere, Franck; Sousa, Pedro M. F.; Rain, Jean-Christophe; Charpentier, Bruno; Cianférani, Sarah; Bandeiras, Tiago M.; Pradet‐Balade, Bérengère; Manival, Xavier; Bertrand, Édouard

doi:10.1038/s41467-018-04431-1

Cited by 68 publications

(176 citation statements)

References 62 publications

(94 reference statements)

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“…SPAG1 contains three TPR domains in its N-terminal end and RPAP3-C-ter domain at its C-terminus ( Figure 2). Moreover, SPAG1 also interacts with Hsp90 and Hsp70 [63].…”

Section: Composition Of R2sp Complex and Function In Dynein Arm Preasmentioning

confidence: 99%

“…The R2SP (RuvBL1-RuvBL2-SPAG1-PIH1D2) complex is related to the R2TP complex, with RPAP3 and PIH1D1 adaptors being replaced by SPAG1 (sperm associated antigen 1) and PIH1D2, respectively [63] (Figure 2). SPAG1 contains three TPR domains in its N-terminal end and RPAP3-C-ter domain at its C-terminus ( Figure 2).…”

Section: Composition Of R2sp Complex and Function In Dynein Arm Preasmentioning

confidence: 99%

“…Data from various organisms indicate that SPAG1 is involved in the pre-assembly of dynein arms [28,63,64]. Knockdown of SPAG1 in Danio rerio caused a phenotype typically observed when motile cilia are dysfunctional (dorsal body axis curvature, and hydrocephalus [28]).…”

Section: Composition Of R2sp Complex and Function In Dynein Arm Preasmentioning

confidence: 99%

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Role of the Novel Hsp90 Co-Chaperones in Dynein Arms’ Preassembly

Fabczak

Osinka

2019

IJMS

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The outer and inner dynein arms (ODAs and IDAs) are composed of multiple subunits including dynein heavy chains possessing a motor domain. These complex structures are preassembled in the cytoplasm before being transported to the cilia. The molecular mechanism(s) controlling dynein arms’ preassembly is poorly understood. Recent evidence suggests that canonical R2TP complex, an Hsp-90 co-chaperone, in cooperation with dynein axonemal assembly factors (DNAAFs), plays a crucial role in the preassembly of ODAs and IDAs. Here, we have summarized recent data concerning the identification of novel chaperone complexes and their role in dynein arms’ preassembly and their association with primary cilia dyskinesia (PCD), a human genetic disorder.

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“…SPAG1 contains three TPR domains in its N-terminal end and RPAP3-C-ter domain at its C-terminus ( Figure 2). Moreover, SPAG1 also interacts with Hsp90 and Hsp70 [63].…”

Section: Composition Of R2sp Complex and Function In Dynein Arm Preasmentioning

confidence: 99%

Section: Composition Of R2sp Complex and Function In Dynein Arm Preasmentioning

confidence: 99%

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Role of the Novel Hsp90 Co-Chaperones in Dynein Arms’ Preassembly

Fabczak

Osinka

2019

IJMS

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“…Although the structure of the RPAP3_C domain of HsCCDC103 could not be solved (see above), an NMR solution structure of the closely related domain from RPAP3 is now available (pdb # 6EZ4; [Maurizy et al, 2018]) and confirms that it is mainly α-helical as predicted previously (King & Patel-King, 2015). Based on this structure, homology models for this 92-residue region from wild type and H154P mutant HsCCDC103 were calculated ( Figure 5).…”

Section: Features Of the Hsccdc103 Rpap3_c Domain And Consequences mentioning

confidence: 65%

“…Homology models of the Hs_CCDC103 RPAP3_C domain and the H154P pathogenic variant were built using Swiss-Model (https:// swissmodel.expasy.org/) using pdb 6EZ4 (Maurizy et al, 2018) as the modeling template. Ramachandran plots of modeled Φ/Ψ angles were generated by Swiss-Model.…”

Section: Bioinformaticsmentioning

confidence: 99%

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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Ciliary dynein arms: Cytoplasmic preassembly, intraflagellar transport, and axonemal docking

Qiu

Roy

2022

Journal Cellular Physiology

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The microtubular scaffold of motile cilia-the axoneme, is decorated with dynein arms, which are large multiprotein complexes essential for ciliary motility. Dynein arms are arranged along the length of the axoneme in a precise repeating pattern, converting chemical energy from ATP hydrolysis into ciliary mechanical movement.How these complicated molecular machines are assembled coordinately and accurately, starting from mere polypeptide chains in the cytoplasm, remains a fascinating yet perplexing question. Rapidly emerging evidence, from multiple studies carried out with different model organisms and with various methodologies, has highlighted the existence of a dedicated assembly pathway. Here, we summarize recent progress made in clarifying the axonemal dynein arm assembly process, focusing on individual assembly steps, including cytoplasmic preassembly, intraflagellar transport, and axonemal docking. K E Y W O R D S dynein arm assembly, dynein arms, motile cilia 1 | INTRODUCTION Motile cilia are microtubule-based organelles that appear as hair-like protrusions on the cell surface and are present in diverse organisms across many evolutionary lineages. The microtubule scaffold of the cilium, the axoneme, is typically organized in a unique "9 + 2" pattern, in which a pair of central microtubules is surrounded by nine peripheral microtubule doublets (each doublet comprising a complete A and an incomplete B tubule) in a circular arrangement (Figure 1) (Ishikawa et al., 2021; Ishikawa, 2017). Importantly, a variety of biological processes, ranging from the free movement of individual cells such as protozoans like Paramecium and spermatozoa to the flow of mucus over the surface of the respiratory tract and circulation of cerebrospinal fluid within the brain ventricular cavities of mammals, all depend on the coordinated beating of motile cilia (F. Zhou & Roy, 2015).Ciliary motility is imparted by molecular motors known as outer and inner dynein arms (ODAs and IDAs, respectively), which are stably attached to the surface of the A tubule of the peripheral axonemal microtubules (Figure 1) (Ishikawa et al., 2021; Ishikawa, 2017). Dynein arms are very large, complex macromolecular assemblies that consist of multiple protein subunits (the estimated size can range from 1-to 2-MDa), overall contributing for ATP catalysis, microtubule binding activity, as well as regulatory input (King, 2016). The core catalytic subunits are comprised of dynein heavy chains (HCs), which have a length of around 4500 amino acid residues (around 500 KDa in size). Additionally, HCs associate and complex with multiple intermediate chains (ICs) and light chains (LCs), forming the dynein motors. Moreover, with the help of docking complexes (DC), dynein motors are able to stably associate with the axonemal microtubules, thereby enabling sliding motion of adjacent microtubule doublets and producing the overall oscillatory movement of the axoneme.Due to their elaborate structure, absence or mutation of even a single structural component of the dynein...

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The RPAP3-Cterminal domain identifies R2TP-like quaternary chaperones

Cited by 68 publications

References 62 publications

Role of the Novel Hsp90 Co-Chaperones in Dynein Arms’ Preassembly

Role of the Novel Hsp90 Co-Chaperones in Dynein Arms’ Preassembly

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

Ciliary dynein arms: Cytoplasmic preassembly, intraflagellar transport, and axonemal docking

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