Fusogenic segments of bovine leukemia virus and simian immunodeficiency virus are interchangeable and mediate fusion by means of oblique insertion in the lipid bilayer of their target cells.

Voneche, V.; Portetelle, Daniel; Kettmann, Richard; Willems, Lucas; Limbach, Keith; Paoletti, Enzo; Ruysschaert, Jean Marie; Burny, Arsène; Brasseur, Robert

doi:10.1073/pnas.89.9.3810

Cited by 83 publications

(71 citation statements)

References 29 publications

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“…Voneche et al demonstrated that replacement of the gp72 cleavage site by RVRG 268 -TP prevented the processing of this envelope glycoprotein by cellular convertases and abolished BLV-induced syncytia formation [4]. In accordance with these cellular data, the results of Fig.…”

Section: In Vitro Cleavage Of Gp72 By Mammalian Convertasessupporting

confidence: 79%

“…Since such a motif is found at the putative processing site of gp72 [4], we first tested the cellular processing of this precursor in LoVo cells which are devoid of furin activity [22]. gesting that endogenous enzymes in both cells can process gp72.…”

Section: Cellular Processing Of Bl V Gp72mentioning

confidence: 99%

“…Systematic comparison of the cleavage site of different viruses revealed the presence of a consensus cleavage sequence RX(R/K)R I identical to that recognized by mammalian subtilisin/kexin-like proteinases [5]. Accordingly, intracellular proteolytic cleavage of gp72 occurs at the proposed internal sequence RVRR|SPV, a process crucial for the infectivity of the virus [4]. So far, a total of seven mammalian subtilisin-like proteases have been identified: furin (also called PACE), PCI (PC3), PC2, PACE4, PC4, PC5-A (PC6-A) and its isoform PC5-B (PC6-B) and the newly discovered PC7 (PC8, LPC or SPC7) (for reviews and updates [6][7][8][9]).…”

Section: Introductionmentioning

confidence: 99%

“…E-mail: jmruyss@ulb.ac.be Abbreviations: VV, vaccinia virus; PC, precursor convertase; RT-PCR, reverse transcriptase polymerase chain reaction; BLV, bovine leukemia virus; gp, glycoprotein; WT, wild type; PBS, phosphate buffer saline; BSA, bovine serum albumin bound gp30 is responsible for anchoring the gp51/gp30 complex. The N-terminal domain of gp30 is involved in membrane fusion [4]. Systematic comparison of the cleavage site of different viruses revealed the presence of a consensus cleavage sequence RX(R/K)R I identical to that recognized by mammalian subtilisin/kexin-like proteinases [5].…”

Section: Introductionmentioning

confidence: 99%

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Comparative processing of bovine leukemia virus envelope glycoprotein gp72 by subtilisin/kexin‐like mammalian convertases

et al. 1997

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Intracellular proteolytic processing of bovine leukemia virus (BLV) envelope glycoprotein precursor (gp72) at the Cterminal end of the RVRR 268 J, site is an essential step for virus infectivity. Subtilisin/kexin-like convertases cleave proproteins at preferred RX(K/R)R J, sites, including those commonly found in viral envelope glycoprotein precursors. We first demonstrated that gp72 is processed into gp51/gp30 in both CV1 cells and the furin-deficient LoVo cells, leading us to compare the ability of mammalian convertases to cleave BLV gp72 in vitro. In contrast to the inability of the neuroendocrine PCI to cleave gp72, the convertases furin, PACE4, PC5-A and PC5-B, which process constitutively secreted precursors, can effectively cleave gp72 into gp51/gp30. N-terminal sequence analysis of the convertasegenerated gp30 demonstrated that cleavage occurs at the in vivoutilized RVRRiSPV site. Such furin-, PACE4-and PC5-mediated processing was completely inhibited by the oiiantitrypsin variant od-PDX. Mutagenesis of the gp72 cleavage site into RVRG-TPV resulted in complete abrogation of gp72 processing by endogenous CV-1 cells and by convertases in vitro. Since our in vitro data suggest a redundancy in the ability of the convertases to cleave gp72, RT-PCR analysis was used to define the convertases expressed in B-lymphocytes, representing one of the major targets of BLV infection. Our data revealed that only furin and the newly discovered PC7 mRNAs are expressed in Raji, B-Jab and LG2 cell lines.

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Section: In Vitro Cleavage Of Gp72 By Mammalian Convertasessupporting

confidence: 79%

Section: Cellular Processing Of Bl V Gp72mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Comparative processing of bovine leukemia virus envelope glycoprotein gp72 by subtilisin/kexin‐like mammalian convertases

et al. 1997

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“…When the peptide is long and hydrophobic enough to dive among the acyl chains, it is likely to perturb their parallel stacking (12). Tilted peptides have been identified in many proteins and protein fragments interacting with lipids such as viral fusion proteins (14), signal peptides of membrane-translocated proteins (15), and proteins involved in lipid metabolism (16). In the latter, they may increase the accessibility of enzymes to hydrophobic substrates (12,17,18).…”

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confidence: 99%

Role of the Lid Hydrophobicity Pattern in Pancreatic Lipase Activity

Thomas

Allouche

Basyn

et al. 2005

Journal of Biological Chemistry

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Pancreatic lipase is a soluble globular protein that must undergo structural modifications before it can hydrolyze oil droplets coated with bile salts. The binding of colipase and movement of the lipase lid open access to the active site. Mechanisms triggering lid mobility are unclear. The *KNILSQIVDIDGI* fragment of the lid of the human pancreatic lipase is predicted by molecular modeling to be a tilted peptide. Tilted peptides are hydrophobicity motifs involved in membrane fusion and more globally in perturbations of hydrophobic/hydrophilic interfaces. Analysis of this lid fragment predicts no clear consensus of secondary structure that suggests that its structure is not strongly sequence determined and could vary with environment. Point mutations were designed to modify the hydrophobicity profile of the [240 -252] fragment and their consequences on the lipase-mediated catalysis were tested. Two mutants, in which the tilted peptide motif was lost, also have poor activity on bile saltcoated oil droplets and cannot be reactivated by colipase. Conversely, one mutant in which a different tilted peptide is created retains colipase dependence. These results suggest that the tilted hydrophobicity pattern of the [240 -252] fragment is neither important for colipase binding to lipase, nor for interfacial binding but is important to trigger the maximal catalytic efficiency of lipase in the presence of bile salt.The pancreatic lipase-colipase complex plays a key role in dietary fat absorption in the intestine by converting triglycerides into more polar products able to cross the brush-border membrane of enterocytes. The lipase is fully active on water-insoluble substrates that form lipid/water interfaces, a phenomenon called interfacial activation. In vivo, oil droplets consist of a bulk substrate phase surrounded by a monolayer of amphiphilic compounds, mainly biliary lipids (phosphatidylcholine, cholesterol and bile salts) that prevent lipase adsorption. To counteract the inhibitory effect of biliary lipids, the pancreas secretes a small protein, colipase, which anchors lipase to the biliary lipid-coated water/ lipid interface. The water-soluble lipase must therefore partition between aqueous and lipid phases before lipolysis can occur.Structural studies (1-3) have shown that lipases possess a two-domain organization, the N-terminal domain bearing the active site and the C-terminal domain bearing the colipase binding site. One specific feature of lipase is the shielding of its catalytic site by a surface loop (lid) controlling the access of the substrate. Therefore, movement of the lid domain is an absolute requirement for the lipase to adopt an active conformation.The role of the lid in lipolysis has been investigated by site-directed mutagenesis, lid exchange, or lid deletion (4 -6). It was first thought to account for the interfacial activation of pancreatic lipase but the presence of a full-length lid in most pancreatic lipase-related proteins that display no interfacial activation rules out this explanation. Actua...

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Type IIA procollagen: Expression in developing chicken limb cartilage and human osteoarthritic articular cartilage

Nah

Swoboda

Birk

et al. 2001

Developmental Dynamics

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Type IIA procollagen is an alternatively spliced product of the type II collagen gene and uniquely contains the cysteine (cys)-rich globular domain in its amino (N)-propeptide. To understand the function of type IIA procollagen in cartilage development under normal and pathologic conditions, the detailed expression pattern of type IIA procollagen was determined in progressive stages of development in embryonic chicken limb cartilages (days 5-19) and in human adult articular cartilage. Utilizing the antibodies specific for the cys-rich domain of the type IIA procollagen N-propeptide, we localized type IIA procollagen in the pericellular and interterritorial matrix of condensing prechondrogenic mesenchyme (day 5) and early cartilage (days 7-9). The intensity of immunostaining was gradually lost with cartilage development, and staining became restricted to the inner layer of perichondrium and the articular cap (day 12). Later in development, type IIA procollagen was re-expressed at the onset of cartilage hypertrophy (day 19). Different from type X collagen, which is expressed throughout hypertrophic cartilage, type IIA procollagen expression was transient and restricted to the zone of early hypertrophy. Immunoelectron microscopic and immunoblot analyses showed that a significant amount of the type IIA procollagen N-propeptide, but not the carboxyl (C)-propeptide, was retained in matrix collagen fibrils of embryonic limb cartilage. This suggests that the type IIA procollagen N-propeptide plays previously unrecognized roles in fibrillogenesis and chondrogenesis. We did not detect type IIA procollagen in healthy human adult articular cartilage. Expression of type IIA procollagen, together with that of type X collagen, was activated by articular chondrocytes in the upper zone of moderately and severely affected human osteoarthritic cartilage, suggesting that articular chondrocytes, which normally maintain a stable phenotype, undergo hypertrophic changes in osteoarthritic cartilage. Based on our data, we propose that type IIA procollagen plays a significant role in chondrocyte differentiation and hypertrophy during normal cartilage development as well as in the pathogenesis of osteoarthritis.

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Fusogenic segments of bovine leukemia virus and simian immunodeficiency virus are interchangeable and mediate fusion by means of oblique insertion in the lipid bilayer of their target cells.

Cited by 83 publications

References 29 publications

Comparative processing of bovine leukemia virus envelope glycoprotein gp72 by subtilisin/kexin‐like mammalian convertases

Comparative processing of bovine leukemia virus envelope glycoprotein gp72 by subtilisin/kexin‐like mammalian convertases

Role of the Lid Hydrophobicity Pattern in Pancreatic Lipase Activity

Type IIA procollagen: Expression in developing chicken limb cartilage and human osteoarthritic articular cartilage

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