Document 0489
 DOCN  M9550489
 TI    Mutations of conserved cysteine residues in the CWLC motif of the
       oncoretrovirus SU protein affect maturation and translocation.
 DT    9505
 AU    Gu J; Parthasarathi S; Varela-Echavarria A; Ron Y; Dougherty JP;
       Department of Molecular Genetics and Microbiology, Robert Wood; Johnson
       Medical School, University of Medicine and Dentistry of; New Jersey,
       Piscataway 08854-5635.
 SO    Virology. 1995 Feb 1;206(2):885-93. Unique Identifier : AIDSLINE
       MED/95159442
 AB    The envelope glycoprotein complex is composed of two polypeptides, an
       external heavily glycosylated polypeptide (SU) and a membrane-spanning
       protein (TM). Together they form a heterodimer on the surface of the
       virion. These proteins are synthesized in the form of a polyprotein
       precursor which is glycosylated and proteolytically processed during its
       maturation in the secretory pathway. A highly conserved stretch of four
       amino acids, CWLC, has been identified in most known oncoretroviral SU
       proteins, about two-thirds of the distance from the amino terminus. To
       study the significance of this sequence for the structure and/or
       function of SU, cysteine to serine mutations were made in
       reticuloendotheliosis virus strain A. Initial studies showed that
       substitution of either one or both cysteines resulted in the production
       of noninfectious virus. Furthermore, immunoprecipitations and
       pulse-chase analysis demonstrated that the mutants yielded envelope
       polyprotein precursors which were stable. However, the polyprotein
       precursors were not proteolytically processed into SU and TM, and
       immunoprecipitations indicate that the immature polyproteins form
       aggregates, suggesting that the mutations interfere with proper folding.
       Although not proteolytically processed, at least one of the mutant
       glycoproteins appeared to be efficiently transported to the cell
       surface. These studies indicate that changing either cysteine residue
       abrogates viral infectivity by affecting folding, inhibiting normal
       maturation of the envelope glycoproteins.
 DE    Amino Acid Sequence  Animal  Bone Neoplasms  Cell Line  Conserved
       Sequence  *Cysteine/METABOLISM  Dogs  Gene Expression  Genes, env
       Glycosylation  Kinetics  Methionine/METABOLISM  Molecular Sequence Data
       Mutagenesis, Site-Directed  Osteosarcoma  Protein Folding
       Retroviridae/METABOLISM/*PHYSIOLOGY/PATHOGENICITY  Support, Non-U.S.
       Gov't  Support, U.S. Gov't, P.H.S.  Transfection  Translation, Genetic
       Tumor Cells, Cultured  Viral Envelope
       Proteins/BIOSYNTHESIS/CHEMISTRY/*METABOLISM  Virion/METABOLISM  JOURNAL
       ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).