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Molecular recognition in the HIV-1 capsid/cyclophilin A complex
S Yoo1, D G Myszka, C Yeh
1Department of Biochemistry, University of Utah, Salt Lake City 84132, USA.
Journal of Molecular Biology
|June 27, 1997
Summary
Human cyclophilin A (CypA) binds HIV-1 capsid protein (CA) via a specific loop. This interaction, crucial for HIV replication, is driven by the Gly89-Pro90 motif, revealing CypA
Area of Science:
- Structural biology
- Virology
- Biochemistry
Background:
- HIV-1 capsid protein (CA) interacts with human cyclophilin A (CypA).
- This interaction is essential for packaging CypA into HIV-1 virions.
- The stoichiometry of CA to CypA in virions is approximately 10:1.
Purpose of the Study:
- To investigate the thermodynamic coupling between CA dimerization and CypA binding.
- To identify key residues and motifs involved in the CA-CypA interaction.
- To understand the role of CypA's active site in HIV-1 replication.
Main Methods:
- Binding affinity measurements of CypA to dimeric CA and monomeric CA151.
- Analysis of the co-crystal structure of the CA151/CypA complex.
- Quantification of energetic contributions of residues within the CA binding loop.
Main Results:
- CypA binds dimeric CA and monomeric CA151 with identical affinities (Kd = 16±4 μM).
- Capsid dimerization and CypA binding are not thermodynamically coupled.
- The Gly89-Pro90 dipeptide within the CA loop is the primary CypA recognition motif.
Conclusions:
- The substoichiometric ratio of CypA in HIV-1 virions is due to the intrinsic stability of the CA/CypA complex.
- Specific residues (Pro85, Val86, His87, Ala88, Pro93) also contribute favorably to CypA binding.
- CypA's active site functions as a sequence-specific protein-binding motif in HIV-1 replication.