CRYSTAL-STRUCTURE OF HUMAN CYCLOPHILIN-A BOUND TO THE AMINO-TERMINAL DOMAIN OF HIV-1 CAPSID

The HIV-1 capsid protein forms the conical core structure at the cente r of the mature virion. Capsid also binds the human peptidyl prolyl is omerase, cyclophilin A, thereby packaging the enzyme into the virion. Cyclophilin A subsequently performs an essential function in HIV-1 rep lication, possibly helping to disassemble the capsid core upon infecti on. We report the 2.36 Angstrom crystal structure of the N-terminal do main of HIV-1 capsid (residues 1-151) in complex with human cyclophili n A. A single exposed capsid loop (residues 85-93) binds in the enzyme 's active site, and Pro-90 adopts an unprecedented trans conformation. The structure suggests how cyclophilin A can act as a sequence-specif ic binding protein and a nonspecific prolyl isomerase. In the crystal lattice, capsid molecules assemble into continuous planar strips. Side by side association of these strips may allow capsid to form the surf ace of the viral core. Cyclophilin A could then function by weakening the association between capsid strips, thereby promoting disassembly o f the viral core.