Deep Structural Analysis of RPAP3 and PIH1D1, Two Components of the HSP90 Co-chaperone R2TP Complex

Henri, Julien; Chagot, Marie-Eve; Bourguet, Maxime; Abel, Yoann; Terral, Guillaume; Maurizy, Chloé; Aigueperse, Christelle; Georgescauld, Florian; Vandermoere, Franck; Saint-Fort, Rénette; Behm‐Ansmant, Isabelle; Charpentier, Bruno; Pradet‐Balade, Bérengère; Verheggen, Céline; Bertrand, Édouard; Meyer, Philippe; Cianférani, Sarah; Manival, Xavier; Quinternet, Marc

doi:10.1016/j.str.2018.06.002

Cited by 41 publications

(74 citation statements)

References 39 publications

(55 reference statements)

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“…RPAP3 ( Figure 2) possesses a C-terminal domain of unknown function (RPAP3-C-ter) and two tandem N-terminal TPRs (tetratricopeptide repeats) domains. The TPR domains enable binding of RPAP3 to Hsp70 [44,45] and Hsp90 (more precisely, to the C-terminal fragment of Hsp90 containing a conserved MEEVD motif/sequence) ( Figure 2) [19,40,46].…”

Section: Composition Of R2tp Complexmentioning

confidence: 99%

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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Section: Composition Of R2tp Complexmentioning

confidence: 99%

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

Fabczak

Osinka

2019

IJMS

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“…Three crystal structures have been reported of intermolecular protein complexes in which one component has a CS domain. The most recently reported complex is between the TPR2 domain of human RPAP3 and the CS domain of human PIH1K1 (PDB entry 6gxz; Henri et al, 2018). Approximately 30 residues at the C-terminus of the RPAP3 protein wrap around the CS domain of PIH1K1, engaging in -structure with strands 3 and 6 on one edge of the -sandwich and strand 1 on the other edge.…”

Section: Cs-b 5 R Interdomain Interactionsmentioning

confidence: 99%

Crystal structures of the naturally fused CS and cytochrome b ₅ reductase (b ₅R) domains of Ncb5or reveal an expanded CS fold, extensive CS–b ₅R interactions and productive binding of the NAD(P)⁺ nicotinamide ring

Benson

Lovell

Mehzabeen

et al. 2019

Acta Cryst Sect D Struct Biol

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PDB references: naturally fused CS and b 5 R domains of human Ncb5or, complex with NAD + , 6mv1; complex with NADP + , 6mv2Supporting information: this article has supporting information at journals.iucr.org/d Crystal structures of the naturally fused CS and cytochrome b 5 reductase (b 5 R) domains of Ncb5or reveal an expanded CS fold, extensive CS-b 5 R interactions and productive binding of the NAD(P) + nicotinamide ring Ncb5or (NADH-cytochrome b 5 oxidoreductase), a cytosolic ferric reductase implicated in diabetes and neurological diseases, comprises three distinct domains, cytochrome b 5 (b 5 ) and cytochrome b 5 reductase (b 5 R) domains separated by a CHORD-Sgt1 (CS) domain, and a novel 50-residue N-terminal region. Understanding how interdomain interactions in Ncb5or facilitate the shuttling of electrons from NAD(P)H to heme, and how the process compares with the microsomal b 5 (Cyb5A) and b 5 R (Cyb5R3) system, is of interest. A high-resolution structure of the b 5 domain (PDB entry 3lf5) has previously been reported, which exhibits substantial differences in comparison to Cyb5A. The structural characterization of a construct comprising the naturally fused CS and b 5 R domains with bound FAD and NAD + (PDB entry 6mv1) or NADP + (PDB entry 6mv2) is now reported. The structures reveal that the linker between the CS and b 5 R cores is more ordered than predicted, with much of it extending the -sandwich motif of the CS domain. This limits the flexibility between the two domains, which recognize one another via a short -sheet motif and a network of conserved side-chain hydrogen bonds, salt bridges and cation-interactions. Notable differences in FAD-protein interactions in Ncb5or and Cyb5R3 provide insight into the selectivity for docking of their respective b 5 redox partners. The structures also afford a structural explanation for the unusual ability of Ncb5or to utilize both NADH and NADPH, and represent the first examples of native, fully oxidized b 5 R family members in which the nicotinamide ring of NAD(P) + resides in the active site. Finally, the structures, together with sequence alignments, show that the b 5 R domain is more closely related to single-domain Cyb5R proteins from plants, fungi and some protists than to Cyb5R3 from animals. research papers Acta Cryst. (2019). D75, 628-638 Benson et al. CS and cytochrome b 5 reductase domains of Ncb5or 629 research papers Acta Cryst. (2019). D75, 628-638 Benson et al. CS and cytochrome b 5 reductase domains of Ncb5or 637

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“…T6 represents a typical case of model extension from homologous models. It is the crystal structure of the human RPAP3(TPR2)-PIH1D1(CS) complex with 522 residues and four chains in the asymmetric unit, but only chains A and C are unique (PDB entry 6gxz; Henri et al, 2018). The highest resolution of the diffraction data is 2.97 Å .…”

Section: Case Studiesmentioning

confidence: 99%

“…Homologous models were searched for in the PDB by the sequences. Two structures, 6fd7 (Henri et al, 2018) and 1gm1 (Walma et al, 2002), were selected as initial models, which have 127 and 94 residues, respectively, but only 56 and 21 residues could match Direct-method-aided partial-structure extension results. the target sequence of chains A and C, respectively.…”

Section: Case Studiesmentioning

confidence: 99%

IPCAS: a direct-method-based pipeline from phasing to model building and refinement for macromolecular structure determination

Ding¹,

Zhang²,

He³

et al. 2020

J Appl Cryst

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A new version (2.0) of the pipeline IPCAS (Iterative Protein Crystal structure Automatic Solution) has been released, in which the program OASIS performs direct-method single-wavelength anomalous diffraction/single isomorphous replacement phasing and direct-method-aided partial-structure extension. IPCAS incorporates the widely used packages CCP4 and PHENIX for locating heavy atoms, density modification, molecular replacement, model building and refinement. Important extensions to the previous version of IPCAS include a resolution screening method for non-crystallographic symmetry searching, an alternate model-building protocol for avoiding premature convergence and direct-method image processing for electron microscopy maps, including singleparticle cryo-EM maps. Moreover, a new graphical user interface is provided for controlling and real-time monitoring of the whole dual-space iterative process, which works as a plugin to CCP4i. Applications of the new IPCAS to difficult cases have yielded promising results, including 'direct-method phasing and fragment extension' from weak anomalous diffraction signal data and 'directmethod-aided partial-structure extension' from low-homology models.

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Deep Structural Analysis of RPAP3 and PIH1D1, Two Components of the HSP90 Co-chaperone R2TP Complex

Cited by 41 publications

References 39 publications

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

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

Crystal structures of the naturally fused CS and cytochrome b ₅ reductase (b ₅R) domains of Ncb5or reveal an expanded CS fold, extensive CS–b ₅R interactions and productive binding of the NAD(P)⁺ nicotinamide ring

IPCAS: a direct-method-based pipeline from phasing to model building and refinement for macromolecular structure determination

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Deep Structural Analysis of RPAP3 and PIH1D1, Two Components of the HSP90 Co-chaperone R2TP Complex

Cited by 41 publications

References 39 publications

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

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

Crystal structures of the naturally fused CS and cytochrome b 5 reductase (b 5R) domains of Ncb5or reveal an expanded CS fold, extensive CS–b 5R interactions and productive binding of the NAD(P)+ nicotinamide ring

IPCAS: a direct-method-based pipeline from phasing to model building and refinement for macromolecular structure determination

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Crystal structures of the naturally fused CS and cytochrome b ₅ reductase (b ₅R) domains of Ncb5or reveal an expanded CS fold, extensive CS–b ₅R interactions and productive binding of the NAD(P)⁺ nicotinamide ring