Structural analysis of the N-terminal domain of the human T-cell leukemia virus capsid protein

The N-terminal domain of the retroviral capsid (CA) protein is one of the l east conserved regions encoded in the genome. Surprisingly, the three-dimen sional structures of the CA from different genera exhibit alpha -helical st ructural features that are highly conserved. The N-terminal residues of the human immunodeficiency virus type 1 (HIV-1) and Rous sarcoma virus (RSV) c apsid proteins form a beta -hairpin. To determine if this feature is conser ved in the retroviral family, we cloned, expressed, purified, and solved th e structure of a N-terminal 134 amino acid fragment (CA(134)) from the huma n T-cell leukemia virus type 1 (HTLV-I) using high resolution nuclear magne tic resonance (NMR) spectroscopy. The CA(134) fragment contains an N-termin al beta -hairpin and a central coiled-coil-like structure composed of six a lpha -helices. The N-terminal Pro1 residue contacts Asp54 in the helical cl uster through a salt bridge. Thus, the beta -hairpin is conserved and the h elical cluster is structurally similar to other retroviral CA domains. Howe ver, although the same Asp residue defines the orientation of the hairpin i n both the HTLV-1 and HIV-1 CA proteins, the HTLV-I hairpin is oriented awa y, rather than towards, the helical core. Significant differences were also detected in the spatial orientation and helical content of the long centra lly located loop connecting the helices in the core. It has been proposed t hat the salt bridge allows the formation of a CA-CA interface that is impor tant for the assembly of the conical cores that are characteristic of HIV-1 . As HTLV-I forms spherical cores, the salt-bridge feature is apparently no t conserved for this function although its role in determining the orientat ion of the beta -hairpin may be critical, along with the central loop. Comp arison of three-dimensional structures is expected to elucidate the relatio nships between the retroviral capsid protein structure and its function. (C ) 2001 Academic Press.