Crystal structure of human T cell leukemia virus type 1 gp21 ectodomain crystallized as a maltose-binding protein chimera reveals structural evolution of retroviral transmembrane proteins

Retroviral entry into cells depends on envelope glycoproteins, whereby rece ptor binding to the surface-exposed subunit triggers membrane fusion by the transmembrane protein (TM) subunit. We determined the crystal structure at 2.5-Angstrom resolution of the ectodomain of gp21, the TM from human T cel l leukemia virus type 1. The gp21 fragment was crystallized as a maltose-bi nding protein chimera, and the maltose-binding protein domain was used to s olve the initial phases by the method of molecular replacement. The structu re of gp21 comprises an N-terminal trimeric coiled coil, an adjacent disulf ide-bonded loop that stabilizes a chain reversal, and a C-terminal sequence structurally distinct from HIV type 1/simian immunodeficiency virus gp41 t hat packs against the coil in an extended antiparallel fashion. Comparison of the gp21 structure with the structures of other retroviral TMs contrasts the conserved nature of the coiled coil-forming region and adjacent disulf ide-bonded loop with the variable nature of the C-terminal ectodomain segme nt. The structure points to these features having evolved to enable the dua l roles of retroviral TMs: conserved fusion function and an ability to anch or diverse surface-exposed subunit structures to the virion envelope and in fected cell surface. The structure of gp21 implies that the N-terminal fusi on peptide is in close proximity to the C-terminal transmembrane domain and likely represents a postfusion conformation.