Catalysis and binding of cyclophilin a with different HIV-1 capsid constructs

被引:35
作者
Bosco, DA [1 ]
Kern, D [1 ]
机构
[1] Brandeis Univ, Dept Biochem, Waltham, MA 02454 USA
关键词
D O I
10.1021/bi049841z
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The prolyl isomerase cyclophilin A (CypA) is required for efficient HIV-1 replication and is incorporated into virions through a binding interaction at the Gly-Pro222 bond located within the capsid domain of the HIV-1 Gag precursor polyprotein (Pr-gag). It has recently been shown that CypA efficiently catalyzes the cis/trans isomerization of Gly-Pro(222) within the isolated N-terminal domain of capsid (CA(N)). To address the proposal that CypA interacts with Gly-Pro sequences in the C-terminal domain of a mature capsid, the interaction between CypA and the natively folded, full-length capsid protein (CA(FL)) has been investigated here using nuclear magnetic resonance spectroscopy. In addition, a fragment of the Prgag protein encoding the full-matrix protein and the N-terminal domain of capsid (MA-CA(N)) has been used to probe the catalytic interaction between CypA and an immature form of the capsid. The results discussed herein strongly suggest that Gly-Pro(222) located within the N-terminal domain of the capsid is the preferential site for CypA binding and catalysis and that catalysis of Gly-Pro(222) is unaffected by maturational processing at the N-terminus of the capsid.
引用
收藏
页码:6110 / 6119
页数:10
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