Structure and self-association of the Rous sarcoma virus capsid protein

Background: The capsid protein (CA) of retroviruses; such as Rous sarcoma v irus (RSV), consists of two independently folded domains. CA functions as p art of a polyprotein during particle assembly and budding and, in addition, forms a shell encapsidating the genomic RNA in the mature, infectious viru s. Results: The structures of the N- and C-terminal domains of RSV CA have bee n determined by X-ray crystallography and solution nuclear magnetic resonan ce (NMR) spectroscopy, respectively. The N-terminal domain comprises seven a helices and a short beta hairpin at the N terminus. The N-terminal domain associates through a small, tightly packed, twofold symmetric interface wi thin the crystal, different from those previously described for other retro viral CAs. The C-terminal domain is a compact bundle of four alpha helices, although the last few residues are disordered. In dilute solution, RSV CA is predominantly monomeric. We show, however, using electron microscopy, th at intact RSV CA can assemble in vitro to form both tubular structures cons tructed from toroidal oligomers and planar monolayers. Both modes of assemb ly occur under similar solution conditions, and both sheets and tubes exhib it long-range order. Conclusions: The tertiary structure of CA is conserved across the major ret roviral genera, yet sequence variations are sufficient to cause change in a ssociative behavior. CA forms the exterior shell of the viral core in all m ature retroviruses. However, the core morphology differs between viruses. C onsistent with this observation, we find that the capsid proteins of RSV an d human immunodeficiency virus type 1 exhibit different associative behavio r in dilute solution and assemble in vitro into different structures.