Important note: Information in this article was accurate in 1999. The state of the art may have changed since the publication date.
The paramyxovirus fusion protein forms an extremely stable core trimer: structural parallels to influenza virus haemagglutinin and HIV-1 gp41.
Mol Membr Biol. 1999 Jan-Mar;16(1):11-9. Unique Identifier : AIDSLINE MED/99265137 Lamb RA; Joshi SB; Dutch RE; Howard Hughes Medical Institute, Northwestern University,; Evanston, IL 60208-3500, USA.
Abstract:
The paramyxovirus fusion (F) protein mediates membrane fusion. The biologically active F protein consists of a membrane distal subunit F2 and a membrane anchored subunit F1. A highly stable structure has been identified comprised of peptides derived from the simian virus 5 (SV5) F1 heptad repeat A, which abuts the hydrophobic fusion peptide (peptide N-1), and the SV5 F1 heptad repeat B, located 270 residues downstream and adjacent to the transmembrane domain (peptides C-1 and C-2). In isolation, peptide N-1 is 47% alpha-helical and peptide C-1 and C-2 are unfolded. When mixed together, peptides N1 + C1 form a thermostable (Tm > 90 degrees C), 82% alpha-helical, discrete trimer of heterodimers (mass 31,300 M(r)) that is resistant to denaturation by 2% SDS at 40 degrees C. The authors suggest that this alpha-helical trimeric complex represents the core most stable form of the F protein that is either fusion competent or forms after fusion has occurred. Peptide C-1 is a potent inhibitor of both the lipid mixing and aqueous content mixing fusion activity of the SV5 F protein. In contrast, peptide N-1 inhibits cytoplasmic content mixing but not lipid mixing, leading to a stable hemifusion state. Thus, these peptides define functionally different steps in the fusion process. The parallels among both the fusion processes and the protein structures of paramyxovirus F proteins, HIV gp41 and influenza virus haemagglutinin are discussed, as the analogies are indicative of a conserved paradigm for fusion promotion among fusion proteins from widely disparate viruses.
Keywords: JOURNAL ARTICLE Dose-Response Relationship, Drug Hemagglutinins, Viral/*CHEMISTRY HIV Envelope Protein gp41/*CHEMISTRY Kinetics Models, Biological Orthomyxoviridae/*CHEMISTRY Paramyxovirus/*CHEMISTRY *Protein Conformation Recombinant Fusion Proteins/*CHEMISTRY Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Temperature 991030
A99A0938
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Important note: Information in this article was accurate in 1999. The state of the art may have changed since the publication date.
