Mechanistic insights into protein folding by the eukaryotic chaperonin complex CCT

Smith, Theobald; Willardson, Barry M.

doi:10.1042/bst20220591

Cited by 9 publications

(4 citation statements)

References 73 publications

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“…Our results showed that the function of CCT Complex is regulated by germ cell-specific STYXL1 and is essential for sperm flagella development. In eukaryotic life, the chaperonin CCT Complex is indispensable for folding the cytoskeletal proteins actin and tubulin along with an estimated 10% of the remaining proteome 61 . Although CCT complex has a certain structure with eight subunits, it is obvious that the functions of the CCT complex are varied and related with lots of diseases.…”

Section: Discussionmentioning

confidence: 99%

STYXL1 regulates CCT complex assembly and flagellar tubulin folding in sperm formation

Chen,

Luo,

et al. 2024

Nat Commun

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Tubulin-based microtubule is a core component of flagella axoneme and essential for sperm motility and male fertility. Structural components of the axoneme have been well explored. However, how tubulin folding is regulated in sperm flagella formation is still largely unknown. Here, we report a germ cell-specific co-factor of CCT complex, STYXL1. Deletion of Styxl1 results in male infertility and microtubule defects of sperm flagella. Proteomic analysis of Styxl1-/- sperm reveals abnormal downregulation of flagella-related proteins including tubulins. The N-terminal rhodanese-like domain of STYXL1 is important for its interactions with CCT complex subunits, CCT1, CCT6 and CCT7. Styxl1 deletion leads to defects in CCT complex assembly and tubulin polymerization. Collectively, our findings reveal the vital roles of germ cell-specific STYXL1 in CCT-facilitated tubulin folding and sperm flagella development.

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Section: Discussionmentioning

confidence: 99%

STYXL1 regulates CCT complex assembly and flagellar tubulin folding in sperm formation

Chen,

Luo,

et al. 2024

Nat Commun

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“…A tailless complex polypeptide 1 ring complex (TRiC), also known as chaperonin containing tailless complex polypeptide 1 (CCT), is a prominent eukaryotic cytoplasmic chaperonin that has several essential cellular functions [ 201 , 202 , 203 ]. TRiC/CCT consists of two oligomeric rings, each composed of eight homologous subunits, termed CCT1-5 in lower eukaryotes and CCTα-θ in mammals [ 201 , 202 , 203 ]. These oligomeric rings associate with each other, forming a central cavity, which serves as a place for protein client folding [ 204 , 205 ].…”

Section: Tric/cct Chaperoninsmentioning

confidence: 99%

Regulation of Epithelial and Endothelial Barriers by Molecular Chaperones

Lechuga,

Marino-Melendez,

Naydenov

et al. 2024

Cells

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The integrity and permeability of epithelial and endothelial barriers depend on the formation of tight junctions, adherens junctions, and a junction-associated cytoskeleton. The establishment of this junction–cytoskeletal module relies on the correct folding and oligomerization of its protein components. Molecular chaperones are known regulators of protein folding and complex formation in different cellular compartments. Mammalian cells possess an elaborate chaperone network consisting of several hundred chaperones and co-chaperones. Only a small part of this network has been linked, however, to the regulation of intercellular adhesions, and the systematic analysis of chaperone functions at epithelial and endothelial barriers is lacking. This review describes the functions and mechanisms of the chaperone-assisted regulation of intercellular junctions. The major focus of this review is on heat shock protein chaperones, their co-chaperones, and chaperonins since these molecules are the focus of the majority of the articles published on the chaperone-mediated control of tissue barriers. This review discusses the roles of chaperones in the regulation of the steady-state integrity of epithelial and vascular barriers as well as the disruption of these barriers by pathogenic factors and extracellular stressors. Since cytoskeletal coupling is essential for junctional integrity and remodeling, chaperone-assisted assembly of the actomyosin cytoskeleton is also discussed.

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“…CCT complex is a conserved multi-subunit complex consisting of two back-to-back rings, each containing eight related but distinct paralogous subunits (named CCT1 to CCT8), forming a complex of approximately 1000 kDa. Eukaryotic CCT complex mediates nascent client peptides folding by encapsulating them in its enclosed central cavity [ 51 , 52 , 53 , 54 , 55 ]. Actin and tubulin captured by PFDc absolutely require CCT for refolding so the cytoskeleton is much more dependent on this biomacromolecules.…”

Section: Dynamic Functions Of Prefoldin Proteins In Plantsmentioning

confidence: 99%

“…Actin and tubulin captured by PFDc absolutely require CCT for refolding so the cytoskeleton is much more dependent on this biomacromolecules. In human, dysfunction of the CCT chaperonin leads to severe disease symptoms such as neurological-related disorders and cancer, largely due to their dysregulation in protein proteostasis and aggregation [ 51 , 54 , 55 , 56 , 57 ]. With similar construction and function, the Arabidopsis CCT complex is also assembled from eight CCT subunits, except that CCT6 has two coding regions that are 96% identical [ 12 , 58 ].…”

Section: Dynamic Functions Of Prefoldin Proteins In Plantsmentioning

confidence: 99%

Prefoldin Subunits and Its Associate Partners: Conservations and Specificities in Plants

Yang,

Zhang,

et al. 2024

Plants

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Prefoldins (PFDs) are ubiquitous co-chaperone proteins that originated in archaea during evolution and are present in all eukaryotes, including yeast, mammals, and plants. Typically, prefoldin subunits form hexameric PFD complex (PFDc) that, together with class II chaperonins, mediate the folding of nascent proteins, such as actin and tubulin. In addition to functioning as a co-chaperone in cytoplasm, prefoldin subunits are also localized in the nucleus, which is essential for transcription and post-transcription regulation. However, the specific and critical roles of prefoldins in plants have not been well summarized. In this review, we present an overview of plant prefoldin and its related proteins, summarize the structure of prefoldin/prefoldin-like complex (PFD/PFDLc), and analyze the versatile landscape by prefoldin subunits, from cytoplasm to nucleus regulation. We also focus the specific role of prefoldin-mediated phytohormone response and global plant development. Finally, we overview the emerging prefoldin-like (PFDL) subunits in plants and the novel roles in related processes, and discuss the next direction in further studies.

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Mechanistic insights into protein folding by the eukaryotic chaperonin complex CCT

Cited by 9 publications

References 73 publications

STYXL1 regulates CCT complex assembly and flagellar tubulin folding in sperm formation

STYXL1 regulates CCT complex assembly and flagellar tubulin folding in sperm formation

Regulation of Epithelial and Endothelial Barriers by Molecular Chaperones

Prefoldin Subunits and Its Associate Partners: Conservations and Specificities in Plants

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