Découverte et structure cristallographique d’une apolipoprotéine humaine

Morales, Renaud; Berna, Anne; Carpentier, Philippe; Contreras‐Martel, Carlos; Renault, Frédérique; Nicodeme, M.; Chesne-Seck, Marie-Laure; Bernier, François; Dupuy, Jérôme; Schaeffer, Christine; Diemer, Hélène; Van-Dorsselaer, Alain; Masson, Patrick; Rochu, Daniel; Chabrière, Éric

doi:10.1016/s0003-4509(07)90023-1

Cited by 9 publications

(3 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…N-terminal sequence of proteins from sheared fractions of the MDR isolates 1 and 13 by Blast Search correspond to PA14–55410 which is orthologous to PA0688 and clusters to the hxc system ( Figure 6 C). We amplified and sequenced the corresponding gene in strain MDR1, and found that the protein encoded by this gene had 90% identity to PA14 55410 from P. aeruginosa PA14, 45.3% identity to PA0688 from P. aeruginosa PAO1, and 64.3% identity to the human plasma phosphate-binding protein HPBP which is classified as a DING protein [ 18 – 20 ]. We therefore named the protein from MDR1 as DING and its respective gene dinG (GenBank Accession number EF616488).…”

Section: Resultsmentioning

confidence: 99%

Structure–Function Aspects of PstS in Multi-Drug–Resistant Pseudomonas aeruginosa

et al. 2008

View full text Add to dashboard Cite

The increasing prevalence of multi-drug–resistant (MDR) strains of Pseudomonas aeruginosa among critically ill humans is of significant concern. In the current study, we show that MDR clinical isolates of P. aeruginosa representing three distinct genotypes that display high virulence against intestinal epithelial cells, form novel appendage-like structures on their cell surfaces. These appendages contain PstS, an extracellular phosphate binding protein. Using anti-PstS antibodies, we determined that the PstS-rich appendages in MDR strains are involved in adherence to and disruption of the integrity of cultured intestinal epithelial cell monolayers. The outer surface–expressed PstS protein was also identified to be present in P. aeruginosa MPAO1, although to a lesser degree, and its role in conferring an adhesive and barrier disruptive phenotype against intestinal epithelial cells was confirmed using an isogenic ΔPstS mutant. Formation of the PstS rich appendages was induced during phosphate limitation and completely suppressed in phosphate-rich media. Injection of MDR strains directly into the intestinal tract of surgically injured mice, a known model of phosphate limitation, caused high mortality rates (60%–100%). Repletion of intestinal phosphate in this model completely prevented mortality. Finally, significantly less outer surface PstS was observed in the MPAO1 mutant ΔHxcR thus establishing a role for the alternative type II secretion system Hxc in outer surface PstS expression. Gene expression analysis performed by RT-PCR confirmed this finding and further demonstrated abundant expression of pstS analogous to pa5369, pstS analogous to pa0688/pa14–55410, and hxcX in MDR strains. Taken together, these studies provide evidence that outer surface PstS expression confers a highly virulent phenotype of MDR isolates against the intestinal epithelium that alters their adhesive and barrier disrupting properties against the intestinal epithelium.

show abstract

Section: Resultsmentioning

confidence: 99%

Structure–Function Aspects of PstS in Multi-Drug–Resistant Pseudomonas aeruginosa

et al. 2008

View full text Add to dashboard Cite

show abstract

“…Indeed, the 40 kDa cotinine receptor, a member of the DING protein family, was purified from rat brains and sequenced [34]. More recently, the 38 kDa apolipoprotein HPBP has been isolated from human blood and its structure was solved using X-ray crystallography [16], [35]. HPBP being a apolipoprotein [16], it could be produced by hepatocytes and could be subsequently secreted in the circulating blood.…”

Section: Discussionmentioning

confidence: 99%

Eukaryotic DING Proteins Are Endogenous: An Immunohistological Study in Mouse Tissues

et al. 2010

View full text Add to dashboard Cite

BackgroundDING proteins encompass an intriguing protein family first characterized by their conserved N-terminal sequences. Some of these proteins seem to have key roles in various human diseases, e.g., rheumatoid arthritis, atherosclerosis, HIV suppression. Although this protein family seems to be ubiquitous in eukaryotes, their genes are consistently lacking from genomic databases. Such a lack has considerably hampered functional studies and has fostered therefore the hypothesis that DING proteins isolated from eukaryotes were in fact prokaryotic contaminants.Principal FindingsIn the framework of our study, we have performed a comprehensive immunological detection of DING proteins in mice. We demonstrate that DING proteins are present in all tissues tested as isoforms of various molecular weights (MWs). Their intracellular localization is tissue-dependant, being exclusively nuclear in neurons, but cytoplasmic and nuclear in other tissues. We also provide evidence that germ-free mouse plasma contains as much DING protein as wild-type.SignificanceHence, data herein provide a valuable basis for future investigations aimed at eukaryotic DING proteins, revealing that these proteins seem ubiquitous in mouse tissue. Our results strongly suggest that mouse DING proteins are endogenous. Moreover, the determination in this study of the precise cellular localization of DING proteins constitute a precious evidence to understand their molecular involvements in their related human diseases.

show abstract

“…A member of the DING family proteins, HPBP, was serendipitously discovered in human plasma while performing structural studies on another target, the HDL-associated human paraoxonase hPON1 [31-33]. The structure topology is similar to the one described for soluble phosphate carriers of the ABC transporter family [32-36] that makes HPBP the first potential phosphate transporter identified in human plasma. Moreover, the association with hPON1 has been hypothesized to be involved in inflammation and atherosclerosis processes [37].…”

Section: Introductionmentioning

confidence: 99%

Human-Phosphate-Binding-Protein inhibits HIV-1 gene transcription and replication

Cherrier

Elias

Jeudy

et al. 2011

Virol J

View full text Add to dashboard Cite

The Human Phosphate-Binding protein (HPBP) is a serendipitously discovered lipoprotein that binds phosphate with high affinity. HPBP belongs to the DING protein family, involved in various biological processes like cell cycle regulation. We report that HPBP inhibits HIV-1 gene transcription and replication in T cell line, primary peripherical blood lymphocytes and primary macrophages. We show that HPBP is efficient in naïve and HIV-1 AZT-resistant strains. Our results revealed HPBP as a new and potent anti HIV molecule that inhibits transcription of the virus, which has not yet been targeted by HAART and therefore opens new strategies in the treatment of HIV infection.

show abstract

Découverte et structure cristallographique d’une apolipoprotéine humaine

Cited by 9 publications

References 40 publications

Structure–Function Aspects of PstS in Multi-Drug–Resistant Pseudomonas aeruginosa

Structure–Function Aspects of PstS in Multi-Drug–Resistant Pseudomonas aeruginosa

Eukaryotic DING Proteins Are Endogenous: An Immunohistological Study in Mouse Tissues

Human-Phosphate-Binding-Protein inhibits HIV-1 gene transcription and replication

Contact Info

Product

Resources

About