Analysis of a peptide inhibitor of paramyxovirus (NDV) fusion using biological assays, NMR, and molecular modeling

John K. Young, Rickey Paige Hicks, George E. Wright, Trudy G. Morrison

Research output: Contribution to journalArticle

81 Citations (Scopus)

Abstract

To investigate the molecular mechanisms involved in paramyxovirus- induced cell fusion, the function and structure of a peptide with a 20- amino-acid sequence from the leucine zipper region (heptad repeat region 2) of the Newcastle disease virus fusion protein (F) were characterized. A peptide with the sequence ALDKLEESNSKLDKVNVKLT (amino acids 476-497 of the F protein) was found to inhibit syncytia formation after virus infection and after transfection of Cos cells with the HN (hemagglutinin-neuraminidase) and F protein cDNAs. Using an F protein gene that requires addition of exogenous trypsin for cleavage, it was shown that the peptide exerted its inhibitory effect prior to cleavage. The three-dimensional conformation of the peptide in aqueous solution was determined through the use of NMR and molecular modeling. Results showed that peptide formed a helix with properties between an α-helix and a 310-helix and that leucine residues aligned along one face of the helix. Side chain salt bridges and hydrogen bonds likely contributed to the stability of the peptide secondary structure. Analysis of the aqueous solution conformation of the peptide suggested mechanisms for specificity of interaction with the intact F protein.

Original languageEnglish (US)
Pages (from-to)291-304
Number of pages14
JournalVirology
Volume238
Issue number2
DOIs
StatePublished - Nov 24 1997

Fingerprint

Biological Assay
Peptides
Amino Acid Sequence
Proteins
Viral Fusion Proteins
Leucine Zippers
Newcastle disease virus
Cell Fusion
Hemagglutinins
Neuraminidase
Virus Diseases
Giant Cells
Leucine
Trypsin
Transfection
Hydrogen
Complementary DNA
Salts

Keywords

  • Fusion
  • Molecular modeling
  • NDV
  • NMR
  • Paramyxovirus
  • Peptide

ASJC Scopus subject areas

  • Virology

Cite this

Analysis of a peptide inhibitor of paramyxovirus (NDV) fusion using biological assays, NMR, and molecular modeling. / Young, John K.; Hicks, Rickey Paige; Wright, George E.; Morrison, Trudy G.

In: Virology, Vol. 238, No. 2, 24.11.1997, p. 291-304.

Research output: Contribution to journalArticle

Young, John K. ; Hicks, Rickey Paige ; Wright, George E. ; Morrison, Trudy G. / Analysis of a peptide inhibitor of paramyxovirus (NDV) fusion using biological assays, NMR, and molecular modeling. In: Virology. 1997 ; Vol. 238, No. 2. pp. 291-304.
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