TY - JOUR
T1 - The paramyxovirus fusion protein forms an extremely stable core trimer
T2 - Structural parallels to influenza virus haemagglutinin and HIV-1 gp41
AU - Lamb, Robert A.
AU - Joshi, Sangeeta Bagai
AU - Dutch, Rebecca Ellis
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 1999
Y1 - 1999
N2 - 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% α-helical and peptide C-1 and C-2 are unfolded. When mixed together, peptides N1+C1 form a thermostable (T(m) > 90°C), 82% α-helical, discrete trimer of heterodimers (mass 31,300 M(r)) that is resistant to denaturation by 2% SDS at 40°C. The authors suggest that this α-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.
AB - 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% α-helical and peptide C-1 and C-2 are unfolded. When mixed together, peptides N1+C1 form a thermostable (T(m) > 90°C), 82% α-helical, discrete trimer of heterodimers (mass 31,300 M(r)) that is resistant to denaturation by 2% SDS at 40°C. The authors suggest that this α-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.
KW - Fusion
KW - Membranes
KW - Paramyxovirus
KW - Peptides
KW - Viruses
UR - http://www.scopus.com/inward/record.url?scp=0032935886&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0032935886&partnerID=8YFLogxK
U2 - 10.1080/096876899294715
DO - 10.1080/096876899294715
M3 - Article
C2 - 10332733
AN - SCOPUS:0032935886
SN - 0968-7688
VL - 16
SP - 11
EP - 19
JO - Molecular Membrane Biology
JF - Molecular Membrane Biology
IS - 1
ER -