Comparative Large Scale Characterization of Plant versus Mammal Proteins Reveals Similar and Idiosyncratic N-α-Acetylation Features

Bienvenut, Willy V.; Sumpton, David; Martinez, Aude; Lilla, Sérgio; Espagne, Christelle; Meinnel, Thierry; Giglione, Carmela

doi:10.1074/mcp.m111.015131

Cited by 159 publications

(213 citation statements)

References 87 publications

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“…In all four TAILS experiments, there was a striking preference for small (alanine, serine) or acidic (aspartate, glutamate) residues in P1Ј and, to a lesser extent, P2Ј. This profile bears close resemblance to the recently presented N-␣ acetylation pattern from human A2780 cells (94). Thus we have provided experimental evidence that mice share a prototypical N-␣ acetylation pattern.…”

Section: N-terminal Protein Acetylation Corresponds To Prototypicalmentioning

confidence: 53%

Deletion of Cysteine Cathepsins B or L Yields Differential Impacts on Murine Skin Proteome and Degradome

Tholen

Biniossek

Gansz

et al. 2013

Molecular & Cellular Proteomics

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Numerous studies highlight the fact that concerted proteolysis is essential for skin morphology and function. The cysteine protease cathepsin L (Ctsl) has been implicated in epidermal proliferation and desquamation, as well as in hair cycle regulation. In stark contrast, mice deficient in cathepsin B (Ctsb) do not display an overt skin phenotype. To understand the systematic consequences of deleting Ctsb or Ctsl, we determined the protein abundances of >1300 proteins and proteolytic cleavage events in skin samples of wild-type, Ctsb ؊/؊ , and Ctsl ؊/؊ mice via mass-spectrometry-based proteomics. Both protease deficiencies revealed distinct quantitative changes in proteome composition. Ctsl Cathepsins B and L are ubiquitously expressed papain-like cysteine proteases belonging to the C1a papain family (clan CA), with 11 members in humans (1) and 18 members in mice (2). Most cysteine cathepsins like cathepsin L are endopeptidases, whereas cathepsin B shows both endopeptidase and carboxydipeptidase activity (3). Mainly localized in the endosomal/lysosomal compartment, cathepsins have traditionally been thought to play important roles in lysosomal protein turnover. Additional specific functions have been postulated that link cathepsins to different physiological and pathological processes.Studies using cathepsin L (Ctsl)-gene-deficient mice 1 revealed an important role of Ctsl in cardiac homeostasis (4 -6) and a contribution of Ctsl to MHC II-mediated antigen presentation (7, 8) and prohormone processing (9, 10). In a mouse model of pancreatic neuroendocrine cancer, Ctsl promoted tumor growth and invasiveness (11,12). In stark contrast, Ctsl was found to attenuate tumor progression in mouse models of skin cancer, highlighting the context-specific function of this protease (13,14).The most prominent phenotype of Ctsl-deficient mice is periodic hair loss together with epidermal hyperplasia, acanthosis, and hyperkeratosis (15). These alterations in skin morphology are assumed to be keratinocyte specific, as controlled re-expression of Ctsl under a keratin 14 promoter Research

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Section: N-terminal Protein Acetylation Corresponds To Prototypicalmentioning

confidence: 53%

Deletion of Cysteine Cathepsins B or L Yields Differential Impacts on Murine Skin Proteome and Degradome

Tholen

Biniossek

Gansz

et al. 2013

Molecular & Cellular Proteomics

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“…The earliest N-terminal modifications actually correspond to cotranslational events involving excision of the first Met residue (NME), NAC of the NME-unmasked N-terminal residue, and specific lipidations, including MYR. Although rarer, posttranslational NAC or MYR have been described on specific substrates (Zha et al, 2000;Martin et al, 2011;Bienvenut et al, 2012). Despite the remarkable advances in genomics, proteomics, bioinformatics, and cellular imaging, all these modifications have remained difficult to observe in vivo (Meinnel and Giglione, 2008b;Bienvenut et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

“…biocuckoo.org/online.php) to be palmitoylated (PALed). Unlike h-TRXs from subgroups 2 and 3, all h-TRXs of subgroup 1 (yellow box in Figures 1A and 1B) were predicted to undergo NAC, one of the most common protein modifications (Martinez et al, 2008;Bienvenut et al, 2012). Interestingly, all h-TRXs from subgroup 1 showed a highly conserved Ala residue in position 2.…”

Section: Prediction Of N-terminal Acylation Of H-trxs Reveals Phylogementioning

confidence: 99%

“…All TRX sequences were next submitted to the online prediction tool TermiNator (http:// www.isv.cnrs-gif.fr/terminator3), a program that we designed to efficiently predict several N-terminal modifications, such as NME, N-a-acetylation (NAC), MYR, and PAL (Frottin et al, 2006;Martinez et al, 2008). The result ( Figure 1B) reveals that virtually all tested plant h-TRXs are predicted to undergo NME, the first irreversible proteolytic modification affecting >80% of plant proteins (Bienvenut et al, 2012). Surprisingly, we found a modification pattern associated with the subgrouping of h-TRXs that was not limited to NME but extended to N-terminal acylations, (e.g.…”

Section: Prediction Of N-terminal Acylation Of H-trxs Reveals Phylogementioning

confidence: 99%

“…TermiNator3 is a very accurate predictor of NME and NAC (Bienvenut et al, 2012), but its reliability remains limited for MYR (Martinez et al, 2008). In order to confirm our predictions about possible MYR of h-TRXs, we measured the capacity of the N-terminal octapeptides to undergo MYR in vitro in a reconstituted MYR assay Traverso et al, 2013).…”

Section: Subgroups 2 and 3 H-trxs Are N-myred In Vitromentioning

confidence: 99%

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Roles of N-Terminal Fatty Acid Acylations in Membrane Compartment Partitioning:Arabidopsis h-Type Thioredoxins as a Case Study

et al. 2013

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N-terminal fatty acylations (N-myristoylation [MYR] and S-palmitoylation [PAL]) are crucial modifications affecting 2 to 4% of eukaryotic proteins. The role of these modifications is to target proteins to membranes. Predictive tools have revealed unexpected targets of these acylations in Arabidopsis thaliana and other plants. However, little is known about how N-terminal lipidation governs membrane compartmentalization of proteins in plants. We show here that h-type thioredoxins (h-TRXs) cluster in four evolutionary subgroups displaying strictly conserved N-terminal modifications. It was predicted that one subgroup undergoes only MYR and another undergoes both MYR and PAL. We used plant TRXs as a model protein family to explore the effect of MYR alone or MYR and PAL in the same family of proteins. We used a high-throughput biochemical strategy to assess MYR of specific TRXs. Moreover, various TRX-green fluorescent protein fusions revealed that MYR localized protein to the endomembrane system and that partitioning between this membrane compartment and the cytosol correlated with the catalytic efficiency of the N-myristoyltransferase acting at the N terminus of the TRXs. Generalization of these results was obtained using several randomly selected Arabidopsis proteins displaying a MYR site only. Finally, we demonstrated that a palmitoylatable Cys residue flanking the MYR site is crucial to localize proteins to micropatching zones of the plasma membrane.

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Structural features of the plant N‐recognin ClpS1 and sequence determinants in its targets that govern substrate selection

et al. 2021

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In the N‐degron pathway of protein degradation of Escherichia coli, the N‐recognin ClpS identifies substrates bearing N‐terminal phenylalanine, tyrosine, tryptophan, or leucine and delivers them to the caseinolytic protease (Clp). Chloroplasts contain the Clp system, but whether chloroplastic ClpS1 adheres to the same constraints is unknown. Moreover, the structural underpinnings of substrate recognition are not completely defined. We show that ClpS1 recognizes canonical residues of the E. coli N‐degron pathway. The residue in second position influences recognition (especially in N‐terminal ends starting with leucine). N‐terminal acetylation abrogates recognition. ClpF, a ClpS1‐interacting partner, does not alter its specificity. Substrate binding provokes local remodeling of residues in the substrate‐binding cavity of ClpS1. Our work strongly supports the existence of a chloroplastic N‐degron pathway.

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Comparative Large Scale Characterization of Plant versus Mammal Proteins Reveals Similar and Idiosyncratic N-α-Acetylation Features

Cited by 159 publications

References 87 publications

Deletion of Cysteine Cathepsins B or L Yields Differential Impacts on Murine Skin Proteome and Degradome

Deletion of Cysteine Cathepsins B or L Yields Differential Impacts on Murine Skin Proteome and Degradome

Roles of N-Terminal Fatty Acid Acylations in Membrane Compartment Partitioning:Arabidopsis h-Type Thioredoxins as a Case Study

Structural features of the plant N‐recognin ClpS1 and sequence determinants in its targets that govern substrate selection

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