1.G.13.2.1 The p15 fusion-associated small transmembrane (FAST)
protein is a nonstructural viral protein that induces cell-cell fusion
and syncytium formation (Top et al. 2012). The small, myristoylated
N-terminal ectodomain of p15 lacks any of the defining features of a typical viral fusion protein. NMR and CD spectroscopy indicated that this small fusion module (residues 68 - 87) comprises a
left-handed polyproline type II (PPII) helix flanked by small,
unstructured N- and C-termini (PDB# 2MNS_A). Individual prolines in the 6-residue
proline-rich motif are tolerant to alanine substitutions, but
multiple substitutions that disrupt the PPII helix eliminate cell-cell
fusion activity. A synthetic p15 ectodomain peptide induces lipid mixing between liposomes. Lipid mixing, liposome
aggregation, and stable peptide-membrane interactions are all dependent
on both the N-terminal myristate and the presence of the PPII helix. A model for the mechanism of action of this viral fusion
peptide, whereby the N-terminal myristate mediates initial, reversible
peptide-membrane binding that is stabilized by subsequent amino
acid-membrane interactions. These interactions induce a biphasic
membrane fusion reaction, with peptide-induced liposome aggregation
representing a distinct, rate-limiting event that precedes membrane
merger. The PPII helix may function to force solvent
exposure of hydrophobic amino acid side chains in the regions flanking
the helix to promote membrane binding, apposition, and fusion (Top et al. 2012). A fusion-inducing lipid packing sensor
(FLiPS) in the cytosolic endodomain in the p15 fusion-associated small transmembrane
(FAST) protein is essential for pore formation during cell-cell fusion and syncytiogenesis (Read et al. 2015). The Myristoylated Polyproline Type Ii Helix Protein of 22 aas (residues
68 - 87 in P15) functions as a fusion peptide during cell-cell membrane
fusion. The 3-d
structure is known (PDB# 2LKW).
|
Accession Number: | Q918V6 |
Protein Name: | Membrane fusion protein p15 |
Length: | 140 |
Molecular Weight: | 15223.00 |
Species: | Baboon orthoreovirus [75888] |
Number of TMSs: | 2 |
Substrate |
small molecules |
---|
1: MGQRHSIVQP PAPPPNAFVE IVSSSTGIII AVGIFAFIFS FLYKLLQWYN RKSKNKKRKE
61: QIREQIELGL LSYGAGVASL PLLNVIAHNP GSVISATPIY KGPCTGVPNS RLLQITSGTA
121: EENTRILNHD GRNPDGSINV