NMR structure of a phosphatidyl‐ethanolamine binding protein from <i>Drosophila</i>

Rautureau, Gilles; Vovelle, F.; Schoentgen, Françoise; Decoville, Martine; Locker, Daniel; Damblon, Christian; Jouvensal, Laurence

doi:10.1002/prot.22682

Cited by 10 publications

(6 citation statements)

References 29 publications

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“…Two functionally important, overlapping fragments present in yeast carboxypeptidase Y inhibitor (PDB code: http://www.rcsb.org/pdb/search/structidSearch.do?structureId=1wpxB ; 594 TDPDAPS) and murine phosphatidylethanolamine binding protein‐2 (PDB code: http://www.rcsb.org/pdb/search/structidSearch.do?structureId=1kn3A ; 70 DPDAPS), where both proteins belong to the phosphatidylethanolamine‐binding protein (PEBP) family, are present in a PEBP family protein of unknown function (PDB code: http://www.rcsb.org/pdb/search/structidSearch.do?structureId=2jyzA ; 61 VDPDAPT) in Drosophila (Fig. A,B).…”

Section: Resultsmentioning

confidence: 99%

“…The matching fragment in 2jyzA, which has no inferred annotation, is present in a cavity corresponding to the putative binding site. The protein has been said to be a member of the PEBP family on the basis of sequence analysis and overall fold . A similar function (phopholipid binding) may be proposed for it based on overall sequence and fold analysis, as well as the presence of the conserved, functionally important cis ‐fragment.…”

Section: Resultsmentioning

confidence: 99%

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Identifying functionally important cis‐peptide containing segments in proteins and their utility in molecular function annotation

2014

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Cis-peptide embedded segments are rare in proteins but often highlight their important role in molecular function when they do occur. The high evolutionary conservation of these segments illustrates this observation almost universally, although no attempt has been made to systematically use this information for the purpose of function annotation. In the present study, we demonstrate how geometric clustering and level-specific Gene Ontology molecular-function terms (also known as annotations) can be used in a statistically significant manner to identify cis-embedded segments in a protein linked to its molecular function. The present study identifies novel cis-peptide fragments, which are subsequently used for fragmentbased function annotation. Annotation recall benchmarks interpreted using the receiver-operator characteristic plot returned an area-under-curve > 0.9, corroborating the utility of the annotation method. In addition, we identified cis-peptide fragments occurring in conjunction with functionally important trans-peptide fragments, providing additional insights into molecular function. We further illustrate the applicability of our method in function annotation where homology-based annotation transfer is not possible. The findings of the present study add to the repertoire of function annotation approaches and also facilitate engineering, design and allied studies around the cis-peptide neighborhood of proteins.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Identifying functionally important cis‐peptide containing segments in proteins and their utility in molecular function annotation

2014

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“…In the mouse, there are three known active RKIP genes: RKIP-1 which is ubiquitously expressed, RKIP-2, whose expression is limited to testes [8,9], and mRKIP-4, a homolog of hPEBP4 located on mouse chromosome 19, whose expression is limited to retinal ganglion cells of the eye [10]. The fruit fly genome encodes six different paralogs of RKIP, all of which appear to be actively transcribed [11]. The gene also has been found in nematodes [12,13], parasites [14] and plants [15,16].…”

Section: The Rkip-1 Gene and Proteinmentioning

confidence: 99%

“…In the nematode, RKIP-1 is present in membranes shed from cell surfaces, suggesting that it has a role in protecting the worm from detection by the host immune system. Drosophila RKIP-1 isoforms [11] have been localized in the lumen of olfactory hairs and in antennae, where they appear to be involved in odorant binding [6]. In plants, RKIP-1 has a role in shoot growth and flowering [17].…”

Section: The Rkip-1 Gene and Proteinmentioning

confidence: 99%

Signaling crossroads: The function of Raf kinase inhibitory protein in cancer, the central nervous system and reproduction

Kłysik

Theroux

Sedivy

et al. 2008

Cellular Signalling

101

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The Raf kinase inhibitory protein 1 (RKIP-1) and its orthologs are conserved throughout evolution and widely expressed in eukaryotic organisms. In its non-phosphorylated form RKIP-1 negatively regulates the Raf/MEK/ERK pathway by interfering with the activity of Raf-1. In its phosphorylated state, RKIP-1 dissociates from Raf-1 and inhibits GRK-2, a negative regulator of G-protein coupled receptors (GPCRs). Available data indicate that the phosphorylation of RKIP-1 by PKC can stimulate both the Raf/MEK/ERK and GPCR pathways. RKIP-1 has also been implicated as a negative regulator of the NF-kappaB pathway. Recent studies have shown that phosphorylated RKIP-1 binds to the centrosomal and kinetochore regions of metaphase chromosomes, where it may be involved in regulating the partitioning of chromosomes and the progression through mitosis. The collective evidence indicates that RKIP-1 regulates the activity and mediates the crosstalk between several important cellular signaling pathways. A variety of ablative interventions suggest that reduced RKIP-1 function may influence metastasis, angiogenesis, resistance to apoptosis, and genome integrity. Attenuation of RKIP-1 may also affect cardiac and neurological functions, spermatogenesis, sperm decapacitation, and reproductive behavior. In this review, the role of RKIP-1 in cellular signaling, and especially its functions revealed using a mouse knockout model, are discussed.

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“…However, it is difficult to separate their desirable effects on cell proliferation from undesirable effects such as proapoptotic activity. We therefore considered the expression of nonmammalian PEBPs, lacking the conserved motifs of mammalian PEBP1 and PEBP4, as a means to enhance cell proliferation without triggering senescence or apoptosis (Ahn et al, 2006; Hanzawa et al, 2005; Harig et al, 2012; Ho & Weigel, 2014; Rautureau et al, 2010; Reumer et al, 2009; Taoka et al, 2011; Wickland & Hanzawa, 2015). Initially, we compared the human proteins PEBP1 (also known as Raf kinase inhibitory protein, RKIP) and PEBP4, two plant homologs (the tobacco developmental regulators NtFT2 and NtFT4), and the fruit fly homologs CG10298 and CG18594 in MCF‐7 breast cancer cells, because these cells have previously been used to characterize PEBP activity (Hagan et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

The tobacco phosphatidylethanolamine‐binding protein NtFT4 simultaneously improves vitality, growth, and protein yield in human cells

Kronenberg

Schrödter

Noll

et al. 2021

Biotech & Bioengineering

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The production of biopharmaceutical proteins in mammalian cells by transient expression or stable transformation requires robust and viable cells. Cell line engineering must therefore balance improved cell growth and viability with high productivity. We tested the ability of nonmammalian phosphatidylethanolamine‐binding proteins to enhance cell proliferation in monolayers and suspension cultures. The tobacco protein NtFT4 improved the proliferation of multiple human cell lines. Viable cell density is usually impaired by efficient transfection, but we found that the number of HEK‐293TNtFT4 cells at the peak of protein expression was twice that of standard HEK‐293T cells, and the antibody yield increased by approximately one‐third. Improved growth and viability were observed in different cell lines, in different culture media, and also after transient transfection, suggesting the beneficial trait is consistent and transferable. Additional modifications could boost the productivity of high‐density HEK‐293TNtFT4 cells even further as we showed for a fluorescent marker protein and recombinant antibody expressed in monolayer cultures. The HEK‐293TNtFT4 cell line provides a new human model platform that increases cell proliferation, also achieving a fundamental improvement in recombinant protein expression.

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NMR structure of a phosphatidyl‐ethanolamine binding protein from Drosophila

Cited by 10 publications

References 29 publications

Identifying functionally important cis‐peptide containing segments in proteins and their utility in molecular function annotation

Identifying functionally important cis‐peptide containing segments in proteins and their utility in molecular function annotation

Signaling crossroads: The function of Raf kinase inhibitory protein in cancer, the central nervous system and reproduction

The tobacco phosphatidylethanolamine‐binding protein NtFT4 simultaneously improves vitality, growth, and protein yield in human cells

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