The interaction network of the chaperonin CCT

Dekker, Carien; Stirling, Peter C.; McCormack, Elizabeth A.; Filmore, Heather; Paul, Angela; Brost, Renée L.; Costanzo, Michael; Boone, Charles; Willison, Keith R.

doi:10.1038/emboj.2008.108

Cited by 198 publications

(222 citation statements)

References 52 publications

(97 reference statements)

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“…The group II eukaryotic chaperonin containing t-complex polypeptide 1 (CCT/ TRiC) also seems to have a specialized role in vivo in the folding of actin (4), tubulin (5), and other essential proteins, including regulators of cell division and cytoskeleton formation (6)(7)(8), despite seeming to possess broad binding specificity (6). The list of members in the CCT interactome is, however, not yet fully established, and the conditions for entry into this exclusive club remain poorly understood.…”

mentioning

confidence: 99%

Interactions of subunit CCT3 in the yeast chaperonin CCT/TRiC with Q/N-rich proteins revealed by high-throughput microscopy analysis

Nadler-Holly¹,

Breker²,

Gruber³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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The eukaryotic chaperonin containing t-complex polypeptide 1 (CCT/TRiC) is an ATP-fueled machine that assists protein folding. It consists of two back-to-back stacked rings formed by eight different subunits that are arranged in a fixed permutation. The different subunits of CCT are believed to possess unique substrate binding specificities that are still mostly unknown. Here, we used highthroughput microscopy analysis of yeast cells to determine changes in protein levels and localization as a result of a Glu to Asp mutation in the ATP binding site of subunits 3 (CCT3) or 6 (CCT6). The mutation in subunit CCT3 was found to induce cytoplasmic foci termed P-bodies where mRNAs, which are not translated, accumulate and can be degraded. Analysis of the changes in protein levels and structural modeling indicate that P-body formation in cells with the mutation in CCT3 is linked to the specific interaction of this subunit with Gln/Asn-rich segments that are enriched in many P-body proteins. An in vitro gel-shift analysis was used to show that the mutation in subunit CCT3 interferes with the ability of CCT to bind a Gln/Asn-rich protein aggregate. More generally, the strategy used in this work can be used to unravel the substrate specificities of other chaperone systems. molecular chaperones | polyQ proteins | protein mis-folding | protein aggregation | high-content analysis C haperonins are ATP-dependent protein-folding machines that are present in all kingdoms of life. They consist of two back-toback stacked oligomeric rings with a cavity at each end, where protein substrate binding and folding take place (for reviews see refs. 1 and 2). The chaperonins can be divided into two groups: group I, found in the bacterial cytoplasm (e.g., GroEL in Escherichia coli), mitochondria, and chloroplasts; and group II found in archaea and the eukaryotic cytosol. Numerous studies have shown that the group I chaperonin GroEL can facilitate the folding of a large number of different proteins in vitro, although its role in the cell is much more limited (for review see ref.3). The group II eukaryotic chaperonin containing t-complex polypeptide 1 (CCT/ TRiC) also seems to have a specialized role in vivo in the folding of actin (4), tubulin (5), and other essential proteins, including regulators of cell division and cytoskeleton formation (6-8), despite seeming to possess broad binding specificity (6). The list of members in the CCT interactome is, however, not yet fully established, and the conditions for entry into this exclusive club remain poorly understood.An important distinction between group I and group II chaperonins is that the former consist of homo-oligomeric rings, whereas the latter usually consist of hetero-oligomeric rings that contain two or three different subunits in the case of many archaeal chaperonins and eight different subunits in the case of CCT. The eight subunits of CCT are arranged in a defined permutation (9), and the orientation of the two rings of CCT with respect to each other is also fixed (10). CCT's heter...

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confidence: 99%

Interactions of subunit CCT3 in the yeast chaperonin CCT/TRiC with Q/N-rich proteins revealed by high-throughput microscopy analysis

Nadler-Holly¹,

Breker²,

Gruber³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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“…2A and Dataset S1). As expected, this network contains proteins previously shown to interact with one or more NuA4 subunits, such as histone proteins H4 (Hhf1), H2A (Hta1 and Hta2), H2B (Htb2), and H3 (Hht1) (19); stress-responsive transcription factors (Msn2, Msn4, and Yap1) (20); subunits of the Chaperonin Containing Tcp1 (CCT) complex (Tcp1, Cct8, Cct4) (21); and the 14-3-3 protein Bmh1 (22 (26)] ( Fig. 2A).…”

Section: Mchip-kat-ms a Methods To Map Protein Interactions And Acetymentioning

confidence: 99%

mChIP-KAT-MS, a method to map protein interactions and acetylation sites for lysine acetyltransferases

Mitchell

Huard

Cotrut

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Significance Recent proteomic studies have revealed that lysine acetylation is a global and ubiquitous posttranslational modification. However, in the vast majority of cases the lysine acetyltransferases (KATs) responsible for individual modifications remain unknown. Here we present a unique methodology that connects KATs to their substrates. To validate the methodology, we use the yeast KAT nucleosome acetyltransferase of histone H4 (NuA4) and identify both protein interactions and acetylation targets. Importantly, this methodology can be applied to any KAT and should aid in the linking of KATs to their cellular targets.

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“…CCT is a hetero-oligomeric complex formed by two rings connected back-to-back, each composed of eight distinct subunits (CCTa-CCTz) (43). It is now well established that the CCT complex mediates the folding, driven by ATP binding and hydrolysis, of a wide range of newly synthesized proteins (44) and that tubulins (a, b and g) (45)(46)(47) and actin (48,49) are its quantitatively major substrates.…”

Section: The Tubulin Folding Pathway: An Overviewmentioning

confidence: 99%

Revisiting the tubulin folding pathway: new roles in centrosomes and cilia

Gonçalves¹,

Tavares²,

Carvalhal³

et al. 2010

BioMolecular Concepts

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Centrosomes and cilia are critical eukaryotic organelles which have been in the spotlight in recent years given their implication in a myriad of cellular and developmental processes. Despite their recognized importance and intense study, there are still many open questions about their biogenesis and function. In the present article, we review the existing data concerning members of the tubulin folding pathway and related proteins, which have been identified at centrosomes and cilia and were shown to have unexpected roles in these structures.

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The interaction network of the chaperonin CCT

Cited by 198 publications

References 52 publications

Interactions of subunit CCT3 in the yeast chaperonin CCT/TRiC with Q/N-rich proteins revealed by high-throughput microscopy analysis

Interactions of subunit CCT3 in the yeast chaperonin CCT/TRiC with Q/N-rich proteins revealed by high-throughput microscopy analysis

mChIP-KAT-MS, a method to map protein interactions and acetylation sites for lysine acetyltransferases

Revisiting the tubulin folding pathway: new roles in centrosomes and cilia

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