MANOSK: A graphics program for analyzing and modeling molecular structure and functions

Cherfils, Jacqueline; Vaney, M.C.; Morize, Isabelle; Surcouf, E.; Colloc’h, N.; Mornon, Jean‐Paul

doi:10.1016/0263-7855(88)80068-7

Cited by 38 publications

(16 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Three-dimensional manipulations were performed with the MANOSK program [22], run on a Vax computer connected to an Evans and Sutherland terminal PS390. Crystallographic data were taken from the Protein Data Bank [23].…”

Section: Methodsmentioning

confidence: 99%

Identification of functional sites on bovine leukemia virus envelope glycoproteins using structural and immunological data

Callebaut

Portetelle

Burny

et al. 1994

European Journal of Biochemistry

View full text Add to dashboard Cite

Sequence analysis using the sensitive hydrophobic cluster analysis method shows that the bovine leukemia virus envelope glycoproteins conserve the general organization of the influenza hemagglutinin into a 'stem', containing the external part of the transmembrane glycoprotein and the Nterminal and C-terminal parts of the external glycoprotein, and a 'head', containing only external glycoprotein residues. However, our analysis suggests, for the first time, that the bovine leukemia virus envelope head will not adopt the typical 'jelly-roll' fold of the influenza A hemagglutinin head, but most likely folds into another type of 'Greek-key' structure corresponding to the overall topology of constant immunoglobulin domains. We constructed a three-dimensional model for the bovine leukemia virus envelope head by homology modeling using the crystal structure of the human histocompatibility antigen HLA-A2 a3 domain. Furthermore, we propose a general model for the oligomeric organization of this head, based on the hemagglutinin trimer. The proposed structural organization of bovine leukemia virus external glycoprotein is further supported by antipeptide and monoclonal antibody reactivities. Our modeling study suggests that the loops of the two neutralizing peptides located in the head are adjacent at the top of the domain and define a potential interaction site of the external glycoprotein with its cellular receptor. This site is topologically similar to the binding site of hemagglutinin with its cellular receptor, sialic acid. The other neutralizing peptides are located within a small domain linking the head to the stem.These data are of interest for defining other oncoviral glycoproteins heads and receptor-binding sites.

show abstract

Section: Methodsmentioning

confidence: 99%

Identification of functional sites on bovine leukemia virus envelope glycoproteins using structural and immunological data

Callebaut

Portetelle

Burny

et al. 1994

European Journal of Biochemistry

View full text Add to dashboard Cite

show abstract

“…Typical applications are described in the references mentioned above and in Refs. 33-35. 3D studies 3D molecular studies were performed using the polyvalent MANOSK software [36] on an Evans & Sutherland PS390 display. Table 1 lists the individual amino acid compositions of all the sequences belonging to our two data sets (fusion peptides and reactive centre loops of serpins).…”

Section: Searching In Nr-mips For Segments Harbouring Fusion Peptide mentioning

confidence: 99%

Common prevalence of alanine and glycine in mobile reactive centre loops of serpins and viral fusion peptides: Do prions possess a fusion peptide?

Callebaut

Tasso

Brasseur

et al. 1994

J Computer-Aided Mol Des

View full text Add to dashboard Cite

Serpin reactive centre loops and fusion peptides released by proteolytic cleavage are particularly mobile. Their amino acid compositions reveal a common and unusual abundance of alanine, accompanied by high levels of glycine. These two small residues, which are not simultaneously abundant in stable helices (standard or transmembrane), probably play an important role in mobility. Threonine and valine (also relatively small amino acids) are also abundant in these two kinds of peptides. Moreover, the known 3D structures of an uncleaved serpin reactive centre and a fusion peptide are strikingly similar. Such sequences possess many small residues and are found in several signal peptides and in PrP, a protein associated with spongiform encephalopathies and resembling virus envelope proteins. These properties may be related to the infection mechanisms of these diseases.

show abstract

“…In related proteins, a precise alignment can then be deduced by proceeding outward from the hydrophobic clusters to linker regions where gaps are allowed. Three-dimensional manipulations were performed with the MANOSK program (33), run on an Evans and Sutherland terminal PS390. Crystallographic data were taken from the Protein Data Bank (34).…”

Section: Methodsmentioning

confidence: 99%

Conservative Mutations in the Immunosuppressive Region of the Bovine Leukemia Virus Transmembrane Protein Affect Fusion but Not Infectivity in Vivo

Gatot

Callebaut²,

Mornon³

et al. 1998

Journal of Biological Chemistry

View full text Add to dashboard Cite

Many retroviruses, including bovine leukemia virus (BLV), contain a highly conserved region located about 40 amino acids downstream from the fusion peptide within the sequence of the external domain of the transmembrane (TM) protein. This region is notably thought to be involved in the presentation of the NH 2 -terminal peptide to allow cell fusion. By using hydrophobic cluster analysis and by analogy with the influenza A hemagglutinin structures, the core of the TM structure including this particular region was predicted to consist, in the BLV and other retroviral envelope proteins, of an ␣-helix followed by a loop region, both docked against a subsequent ␣-helix that forms a triple-stranded coiled coil. The loop region could undergo, as in hemagglutinin, a major refolding into an ␣-helix integrating the coiled coil structure and putting the fusion peptide to one tip of the molecule. Based on this model, we have identified amino acids that may be essential to the BLV TM structure, and a series of mutations were introduced in the BLV env gene of an infectious molecular clone. A first series of mutations was designed to disturb the coiled coil structure (substitutions with proline residues), whereas others would maintain the general TM structure. When expressed by Semliki Forest virus recombinants, all the mutated envelope proteins were stable and efficiently synthesized in baby hamster kidney cells. Both proline-substituted and conservative mutants were strongly affected in their capacity to fuse to CC81 indicator cells. In addition, it appeared that the integrity of the TM coiled coil structure is essential for envelope protein multimerization, as analyzed by metrizamide gradient centrifugation. Finally, to gain insight into the role of this coiled coil in the infectious potential of BLV in vivo, the mutated TM genes were introduced in an infectious and pathogenic molecular clone and injected into sheep. It appeared that only the conservative mutations (A60V and A64S) allowed maintenance of viral infectivity in vivo. Since these mutations destroyed the ability to induce syncytia, we conclude that efficient fusion capacity of the recombinant envelopes is not a prerequisite for the infectious potential of BLV in vivo. Viral propagation of these mutants was strongly affected in some of the infected sheep. However, the proviral loads within half of the infected animals (2 out of 2 for A60V and 1 out of 4 for A64S) were close to the wild-type levels. In these sheep, it thus appears that the A60V and A64S mutants propagate efficiently despite being unable to induce syncytia in cell culture.The infectivity of enveloped viruses is thought to be mediated by surface glycoproteins that are responsible for the recognition of the target cell and for the fusion of both viral and cellular membranes (1). The envelope proteins of the retroviruses are composed of the following two subunits: the extracellular (SU) 1 protein that binds to the receptor and the transmembrane (TM) glycoprotein that anchors the envelope complex into t...

show abstract

MANOSK: A graphics program for analyzing and modeling molecular structure and functions

Cited by 38 publications

References 17 publications

Identification of functional sites on bovine leukemia virus envelope glycoproteins using structural and immunological data

Identification of functional sites on bovine leukemia virus envelope glycoproteins using structural and immunological data

Common prevalence of alanine and glycine in mobile reactive centre loops of serpins and viral fusion peptides: Do prions possess a fusion peptide?

Conservative Mutations in the Immunosuppressive Region of the Bovine Leukemia Virus Transmembrane Protein Affect Fusion but Not Infectivity in Vivo

Contact Info

Product

Resources

About