Versatile TPR domains accommodate different modes of target protein recognition and function

Allan, Rudi K.; Ratajczak, Thomas

doi:10.1007/s12192-010-0248-0

Cited by 213 publications

(184 citation statements)

References 156 publications

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“…One arrangement, conserved from protozoa to humans, places a tetratricopeptide repeat (TPR) domain downstream from the FKBP domain (Pratt et al 2004). The TPR domain is a protein-protein interaction module that binds heat shock proteins (HSPs), primarily of the HSP90 family in higher eukaryotes (Pratt 1998;Allan and Ratajczak 2011). Several crystal structures are available that highlight key conserved residues that participate in this interaction (Van Duyne et al 1993;Ward et al 2002).…”

Section: Introductionmentioning

confidence: 99%

shutdown is a component of the Drosophila piRNA biogenesis machinery

Preall¹,

Czech²,

Guzzardo³

et al. 2012

RNA

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In animals, the piRNA pathway preserves the integrity of gametic genomes, guarding them against the activity of mobile genetic elements. This innate immune mechanism relies on distinct genomic loci, termed piRNA clusters, to provide a molecular definition of transposons, enabling their discrimination from genes. piRNA clusters give rise to long, single-stranded precursors, which are processed into primary piRNAs through an unknown mechanism. These can engage in an adaptive amplification loop, the ping-pong cycle, to optimize the content of small RNA populations via the generation of secondary piRNAs. Many proteins have been ascribed functions in either primary biogenesis or the ping-pong cycle, though for the most part the molecular functions of proteins implicated in these pathways remain obscure. Here, we link shutdown (shu), a gene previously shown to be required for fertility in Drosophila, to the piRNA pathway. Analysis of knockdown phenotypes in both the germline and somatic compartments of the ovary demonstrate important roles for shutdown in both primary biogenesis and the ping-pong cycle. shutdown is a member of the FKBP family of immunophilins. Shu contains domains implicated in peptidyl-prolyl cis-trans isomerase activity and in the binding of HSP90-family chaperones, though the relevance of these domains to piRNA biogenesis is unknown.Keywords: piRNAs; transposon silencing; RNAi; FKBP; germ cells INTRODUCTIONEukaryotic genomes are prone to the accumulation of repetitive sequences, including transposable elements, over evolutionary time (McClintock 1953;Kim et al. 1994;Brennecke et al. 2007;Chambeyron et al. 2008;Feschotte 2008). The genomic instability brought about by transposon activity is a double-edged sword. Low levels of transposition can drive evolution in the long term, but loss of control over mobile elements in any individual can threaten reproductive success. Mechanisms for suppressing transposon activation in the germline are therefore both potent and widely conserved (Grimson et al. 2008). In animals, the PIWI-interacting RNA (piRNA) pathway is key to transposon silencing in reproductive tissues (Aravin et al. 2006;Girard et al. 2006;Lau et al. 2006;Vagin et al. 2006;Khurana and Theurkauf 2010;Senti and Brennecke 2010). In Drosophila, piRNAs are active both in the germ cell lineage and in a particular somatic lineage that encysts the germ cells and provides growth and maturation signals piRNA clusters sit at the apex of the pathway and, based upon their sequence content, define transposon targets for repression (Brennecke et al. 2007). piRNA clusters give rise to long, single-stranded transcripts (Brennecke et al. 2007) that are thought to be exported to the cytoplasm and processed into primary piRNAs, most likely in specialized cytoplasmic structures (Saito et al. 2010;Handler et al. 2011). A number of proteins have been implicated in primary piRNA biogenesis and their loading into PIWI-family proteins, including Armitage, Zucchini, Vreteno, and the Yb family (Klattenhoff et al...

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Section: Introductionmentioning

confidence: 99%

shutdown is a component of the Drosophila piRNA biogenesis machinery

Preall¹,

Czech²,

Guzzardo³

et al. 2012

RNA

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“…Although different interaction interfaces between Hsps and co-chaperones exist (2,3), the largest group of co-chaperones interacts with the highly conserved EEVD-COOH motif present in the C-terminal domains of both Hsp70 and Hsp90 (4 -7). These co-chaperones contain so-called tetratricopeptide repeat (TPR) 4 domains (8). TPR domains are present in a variety of proteins and serve as a versatile proteinprotein interaction module (4).…”

mentioning

confidence: 99%

“…These co-chaperones contain so-called tetratricopeptide repeat (TPR) 4 domains (8). TPR domains are present in a variety of proteins and serve as a versatile proteinprotein interaction module (4). TPR domains consist of tandem repeats of a degenerate 34-amino acid motif that folds into two anti-parallel ␣-helices, and tandem arrays of TPR motifs form a saddle-like groove, which is able to accommodate polypeptides from other proteins (7,8).…”

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confidence: 99%

The Assembly and Intermolecular Properties of the Hsp70-Tomm34-Hsp90 Molecular Chaperone Complex

Trčka

Ďurech

Man

et al. 2014

Journal of Biological Chemistry

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“…These proteins are known to act as interaction scaffolds in the formation of multi-protein complexes [5].…”

Section: Discussionmentioning

confidence: 99%

“…Although farnesyltransferase inhibitors (FTIs) are undergoing clinical trials, their antitumor effect has been independent of Ras mutations. The α subunits of prenyltransferases belong to the tetratricopeptide repeat (TPR) superfamily [4,5]. The β subunit of prenyltransferases encompasses the active site, however, it is inactive in the absence of the α subunit [6].…”

Section: Introductionmentioning

confidence: 99%

Mammalian farnesyltransferase α subunit regulates vacuolar protein sorting-associated protein 4A (Vps4A) – dependent intracellular trafficking through recycling endosomes

Kubala

Norwood

Gómez

et al. 2015

Biochemical and Biophysical Research Communications

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The protein farnesyltransferase (FTase) mediates posttranslational modification of proteins with isoprenoid lipids. FTase is a heterodimer and although the β subunit harbors the active site, it requires the α subunit for its activity. Here we explore the other functions of the FTase α subunit in addition to its established role in protein prenylation. We found that in the absence of the β subunit, the α subunit of FTase forms a stable autonomous dimeric structure in solution. We identify interactors of FTase α using mass spectrometry, followed by rapid in vitro analysis using the Leishmania tarentolae cell -free system.

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Versatile TPR domains accommodate different modes of target protein recognition and function

Cited by 213 publications

References 156 publications

shutdown is a component of the Drosophila piRNA biogenesis machinery

shutdown is a component of the Drosophila piRNA biogenesis machinery

The Assembly and Intermolecular Properties of the Hsp70-Tomm34-Hsp90 Molecular Chaperone Complex

Mammalian farnesyltransferase α subunit regulates vacuolar protein sorting-associated protein 4A (Vps4A) – dependent intracellular trafficking through recycling endosomes

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