The cysteine residues of HIV-1 capsid regulate oligomerization and cyclophilin A-induced changes.
Assembly of the HIV-1 virus involves, in part, strong interactions between the capsid (CA) domains of the Gag polyprotein. During maturation, the core of HIV-1 virions undergoes profound morphological changes due primarily to proteolysis of the CA domain from other Gag domains which may allow for more efficient disassembly of the viral core in the early stages of infection. The host protein cyclophilin A (CypA), a cis-trans prolyl isomerase, in some way seems to assist in this assembly/disassembly process. Using an unproteolyzed construct of CA, we show that binding of CypA induces a large-scale conformational change in CA that is independent of its cis-trans prolyl isomerase activity. This change appears to be mediated by Cys-198 of CA since mutation to Ala renders CypA unable to induce this change and alters the kinetics and stability of protein cores that may ultimately result in inefficient disassembly of viral cores. Alternately, mutation of the second CA Cys (C218A) allows for CypA-induced conformational changes but alters the kinetics and morphology of the protein cores that may ultimately result in inefficient assembly of viral cores. These studies show the importance of the CA Cys residues in mediating the contacts needed for viral assembly and disassembly.
Bon Homme
Marjorie
M
Department of Physiology and Biophysics, State University of New York at Stony Brook, New York, USA.
Carter
Carol
C
Scarlata
Suzanne
S
D019943:Amino Acid Substitution; D001665:Binding Sites; D036022:Capsid Proteins / Q000032:analysis / Q000737:chemistry*; D021984:Cyclophilin A / Q000737:chemistry*; D003545:Cysteine / Q000737:chemistry*; D019281:Dimerization; D015497:HIV-1 / Q000378:metabolism*; D007700:Kinetics; D046912:Multiprotein Complexes / Q000032:analysis / Q000737:chemistry; D016297:Mutagenesis, Site-Directed; D011485:Protein Binding; D011994:Recombinant Proteins / Q000032:analysis / Q000737:chemistry; D013329:Structure-Activity Relationship; D019065:Virus Assembly
D036022:Capsid Proteins; D046912:Multiprotein Complexes; D011994:Recombinant Proteins; D021984:Cyclophilin A; D003545:Cysteine