James Crowe
Faculty Member
Last active: 3/31/2019

Examination of a fusogenic hexameric core from human metapneumovirus and identification of a potent synthetic peptide inhibitor from the heptad repeat 1 region.

Miller SA, Tollefson S, Crowe JE, Williams JV, Wright DW
J Virol. 2007 81 (1): 141-9

PMID: 17035305 · PMCID: PMC1797239 · DOI:10.1128/JVI.01243-06

Paramyxoviruses are a leading cause of childhood illness worldwide. A recently discovered paramyxovirus, human metapneumovirus (hMPV), has been studied by our group in order to determine the structural relevance of its fusion (F) protein to other well-characterized viruses utilizing type I integral membrane proteins as fusion aids. Sequence analysis and homology models suggested the presence of requisite heptad repeat (HR) regions. Synthetic peptides from HR regions 1 and 2 (HR-1 and -2, respectively) were induced to form a thermostable (melting temperature, approximately 90 degrees C) helical structure consistent in mass with a hexameric coiled coil. Inhibitory studies of hMPV HR-1 and -2 indicated that the synthetic HR-1 peptide was a significant fusion inhibitor with a 50% inhibitory concentration and a 50% effective concentration of approximately 50 nM. Many viral fusion proteins are type I integral membrane proteins utilizing the formation of a hexameric coiled coil of HR peptides as a major driving force for fusion. Our studies provide evidence that hMPV also uses a coiled-coil structure as a major player in the fusion process. Additionally, viral HR-1 peptide sequences may need further investigation as potent fusion inhibitors.

MeSH Terms (12)

Amino Acid Sequence Antiviral Agents Metapneumovirus Models, Molecular Molecular Sequence Data Peptides Protein Structure, Tertiary Repetitive Sequences, Amino Acid Sequence Alignment Sequence Analysis, Protein Viral Core Proteins Viral Fusion Proteins

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