Structural characterization and unfolding mechanism of human 4F2hc ectodomain

Turnay, Javier; Fort, Joana; Olmo, Nieves; Santiago-Gómez, Angélica; Palacı́n, Manuel; Lizarbe, M.A.

doi:10.1016/j.bbapap.2011.02.010

Cited by 6 publications

(3 citation statements)

References 47 publications

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“…As the protein contains a potential Ca 2+ -binding domain, Ca 2+ -binding will change its conformation of secondary structure which can be detected by CD [34], [35], [36]. CD measurements were carried out on a J-810 Circular Dichroism Spectrometer (Jasco, Japan) with the Jasco Spectra Manager software at room temperature.…”

Section: Methodsmentioning

confidence: 99%

Molecular Characterization of Severin from Clonorchis sinensis Excretory/Secretory Products and Its Potential Anti-apoptotic Role in Hepatocarcinoma PLC Cells

Chen

et al. 2013

PLoS Negl Trop Dis

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BackgroundClonorchiasis, caused by the infection of Clonorchis sinensis (C. sinensis), is a kind of neglected tropical disease, but it is highly related to cholangiocarcinoma and hepatocellular carcinoma (HCC). It has been well known that the excretory/secretory products of C. sinensis (CsESPs) play key roles in clonorchiasis associated carcinoma. From genome and transcriptome of C. sinensis, we identified one component of CsESPs, severin (Csseverin), which had three putative gelsolin domains. Its homologues are supposed to play a vital role in apoptosis resistance of tumour cell.Methodology/Principal FindingsThere was significant similarity in tertiary structures between human gelsolin and Csseverin by bioinformatics analysis. We identified that Csseverin expressed at life stage of adult worm, metacercaria and egg by the method of quantitative real-time PCR and western blotting. Csseverin distributed in vitellarium and intrauterine eggs of adult worm and tegument of metacercaria by immunofluorence assay. We obtained recombinant Csseverin (rCsseverin) and confirmed that rCsseverin could bind with calciumion in circular dichroism spectrum analysis. It was demonstrated that rCsseverin was of the capability of actin binding by gel overlay assay and immunocytochemistry. Both Annexin V/PI assay and mitochondrial membrane potential assay of human hepatocarcinoma cell line PLC showed apoptosis resistance after incubation with different concentrations of rCsseverin. Morphological analysis, apoptosis-associated changes of mitochondrial membrane potential and Annexin V/PI apoptosis assay showed that co-incubation of PLC cells with rCsseverin in vitro led to an inhibition of apoptosis induced by serum-starved for 24 h.Conclusions/SignificanceCollectively, the molecular properties of Csseverin, a molecule of CsESPs, were characterized in our study. rCsseverin could cause obvious apoptotic inhibition in human HCC cell line. Csseverin might exacerbate the process of HCC patients combined with C. sinensis infection.

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Section: Methodsmentioning

confidence: 99%

Molecular Characterization of Severin from Clonorchis sinensis Excretory/Secretory Products and Its Potential Anti-apoptotic Role in Hepatocarcinoma PLC Cells

Chen

et al. 2013

PLoS Negl Trop Dis

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“…The assembly of the two chains occurs at the endoplasmic reticulum (ER) membrane, before glycan processing or Golgi trafficking, since the disulfide-liked heterodimer is detected early after translation in the core-glycosylated form (46). CD98hc probably folds by itself, independent of glycosylation or heterodimer formation (33,74), unlike rBAT (34). By using a flexible linker, CD98hc-ED can interact with either LAT1 or the lipid membrane surface (33) through its positively-charged patch (Fig.…”

Section: Assembly Trafficking and Stabilizationmentioning

confidence: 99%

Cryo-EM structure of the human L-type amino acid transporter 1 in complex with glycoprotein CD98hc

Lee

Wiriyasermkul

Jin

et al. 2019

Nat Struct Mol Biol

127

175

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“…The structures of 4F2hc-ED produced in E. coli (without N -glycosylations) or in mammalian cells ( N -glycosilated), do not show large differences, even near the glycosylation sites, thus indicating that N -glycosilations in 4F2hc are not needed for proper protein folding. Moreover, 4F2hc-ED produced in E. coli shows high stability [ 63 ] and even confers stability to LAT2 when it is solubilized in detergent [ 14 ].…”

Section: Structure Of the Ectodomains Of 4f2hc And Rbatmentioning

confidence: 99%

The Ectodomains of rBAT and 4F2hc Are Fake or Orphan α-Glucosidases

2021

Self Cite

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It is known that 4F2hc and rBAT are the heavy subunits of the heteromeric amino acid transporters (HATs). These heavy subunits are N-glycosylated proteins, with an N-terminal domain, one transmembrane domain and a bulky extracellular domain (ectodomain) that belongs to the α-amylase family. The heavy subunits are covalently linked to a light subunit from the SLC7 family, which is responsible for the amino acid transport activity, forming a heterodimer. The functions of 4F2hc and rBAT are related mainly to the stability and trafficking of the HATs in the plasma membrane of vertebrates, where they exert the transport activity. Moreover, 4F2hc is a modulator of integrin signaling, has a role in cell fusion and it is overexpressed in some types of cancers. On the other hand, some mutations in rBAT are found to cause the malfunctioning of the b0,+ transport system, leading to cystinuria. The ectodomains of 4F2hc and rBAT share both sequence and structure homology with α-amylase family members. Very recently, cryo-EM has revealed the structure of several HATs, including the ectodomains of rBAT and 4F2hc. Here, we analyze available data on the ectodomains of rBAT and 4Fhc and their relationship with the α-amylase family. The physiological relevance of this relationship remains largely unknown.

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Structural characterization and unfolding mechanism of human 4F2hc ectodomain

Cited by 6 publications

References 47 publications

Molecular Characterization of Severin from Clonorchis sinensis Excretory/Secretory Products and Its Potential Anti-apoptotic Role in Hepatocarcinoma PLC Cells

Molecular Characterization of Severin from Clonorchis sinensis Excretory/Secretory Products and Its Potential Anti-apoptotic Role in Hepatocarcinoma PLC Cells

Cryo-EM structure of the human L-type amino acid transporter 1 in complex with glycoprotein CD98hc

The Ectodomains of rBAT and 4F2hc Are Fake or Orphan α-Glucosidases

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