2WLV: Structure Of The N-terminal Capsid Domain Of Hiv-2

TRIMCyps are primate antiretroviral proteins that potently inhibit HIV replication. Here we describe how rhesus macaque TRIMCyp (RhTC) has evolved to target and restrict HIV-2. We show that the ancestral cyclophilin A (CypA) domain of RhTC targets HIV-2 capsid with weak affinity, which is strongly increased in RhTC by two mutations (D66N and R69H) at the expense of HIV-1 binding. These mutations disrupt a constraining intramolecular interaction in CypA, triggering the complete restructuring (>16 A) of an active site loop. This new configuration discriminates between divergent HIV-1 and HIV-2 loop conformations mediated by capsid residue 88. Viral sensitivity to RhTC restriction can be conferred or abolished by mutating position 88. Furthermore, position 88 determines the susceptibility of naturally occurring HIV-1 sequences to restriction. Our results reveal the complex molecular, structural and thermodynamic changes that underlie the ongoing evolutionary race between virus and host.
PDB ID: 2WLVDownload
MMDB ID: 76804
PDB Deposition Date: 2009/6/26
Updated in MMDB: 2009/09
Experimental Method:
x-ray diffraction
Resolution: 1.25  Å
Source Organism:
Similar Structures:
Biological Unit for 2WLV: dimeric; determined by author and by software (PISA)
Molecular Components in 2WLV
Label Count Molecule
Proteins (2 molecules)
GAG Polyprotein
Molecule annotation
GAG Polyprotein
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB