Analysis of a membrane interacting region of herpes simplex virus type 1 glycoprotein H.
Glycoprotein H (gH) of herpes simplex virus type I (HSV-1) is involved in the complex mechanism of membrane fusion of the viral envelope with the host cell. Membrane interacting regions and potential fusion peptides have been identified in HSV-1 gH as well as glycoprotein B (gB). Because of the complex fusion mechanism of HSV-1, which requires four viral glycoproteins, and because there are only structural data for gB and glycoprotein D, many questions regarding the mechanism by which HSV-1 fuses its envelope with the host cell membrane remain unresolved. Previous studies have shown that peptides derived from certain regions of gH have the potential to interact with membranes, and based on these findings we have generated a set of peptides containing mutations in one of these domains, gH-(626-644), to investigate further the functional role of this region. Using a combination of biochemical, spectroscopic, and nuclear magnetic resonance techniques, we showed that the alpha-helical nature of this stretch of amino acids in gH is important for membrane interaction and that the aromatic residues, tryptophan and tyrosine, are critical for induction of fusion.
Galdiero
Stefania
S
Department of Biological Sciences, Division of Biostructures, University of Naples Federico II, Via Mezzocannone 16, 80134, Napoli, Italy.
Falanga
Annarita
A
Vitiello
Mariateresa
M
Raiola
Luca
L
Fattorusso
Roberto
R
Browne
Helena
H
Pedone
Carlo
C
Isernia
Carla
C
Galdiero
Massimiliano
M
D020106:Acrylamide / Q000737:chemistry; D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry; D002942:Circular Dichroism; D015967:Gene Expression Regulation, Viral; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008954:Models, Biological; D008969:Molecular Sequence Data; D009154:Mutation; D010447:Peptide Hydrolases / Q000737:chemistry; D017433:Protein Structure, Secondary; D014364:Tryptophan / Q000737:chemistry; D014759:Viral Envelope Proteins / Q000378:metabolism*
D000596:Amino Acids; D014759:Viral Envelope Proteins; C040495:glycoprotein B, Simplexvirus; C044200:glycoprotein H, herpes simplex virus type 1; D020106:Acrylamide; D014364:Tryptophan; D010447:Peptide Hydrolases