D. Fass et Ps. Kim, DISSECTION OF A RETROVIRUS ENVELOPE PROTEIN REVEALS STRUCTURAL SIMILARITY TO INFLUENZA HEMAGGLUTININ, Current biology, 5(12), 1995, pp. 1377-1383
Background: The amino-acid sequences of retroviral envelope proteins c
ontain a '4-3 hydrophobic repeat', with hydrophobic amino acids spaced
every four and then every three residues, characteristic of sequences
that form coiled coils. The 4-3 hydrophobic repeat is located in the
transmembrane subunit (TM) of the retroviral envelope protein, adjacen
t to the fusion peptide, a region that inserts into the host bilayer d
uring the membrane-fusion process. A 4-3 hydrophobic repeat region in
an analogous position of the influenza hemagglutinin protein is recrui
ted to extend a three-stranded coiled coil during the conformational c
hange to the fusion-competent state. To determine the conformation of
the retroviral TM subunit and the role of the 4-3 hydrophobic repeat,
we constructed soluble peptide models of the envelope protein of Molon
ey murine leukemia virus (MMLV). Results: The region of the MMLV TM pr
otein external to the lipid envelope (the ectodomain) contains a stabl
y folded, trimeric, protease-resistant core. As predicted, an alpha-he
lical segment spans the 4-3 repeat. A cysteine-rich region carboxy-ter
minal to the 4-3 repeat confers a dramatic increase in stability and d
isplays a unique disulfide bonding pattern. Conclusions: Our results d
emonstrate that the MMLV TM subunit can fold into a stable and distinc
t species in the absence of the receptor-binding 'surface' co-subunit
(SU) of the envelope complex. As the SU subunit is readily shed fi-om
the surface of the virus, we conclude that the TM subunit structure fo
rms the core of the MMLV membrane-fusion machinery, and that this stru
cture, like the fusion-active conformation of influenza hemagglutinin,
contains a three-stranded coiled coil adjacent to the fusion peptide.