Solution structure of the HIV-1 integrase-binding domain in LEDGF/p75.
Lens epithelium-derived growth factor (LEDGF)/p75 is the dominant binding partner of HIV-1 integrase (IN) in human cells. We have determined the NMR structure of the integrase-binding domain (IBD) in LEDGF and identified amino acid residues essential for the interaction. The IBD is a compact right-handed bundle composed of five alpha-helices. Based on folding topology, the IBD is structurally related to a diverse family of alpha-helical proteins that includes eukaryotic translation initiation factor eIF4G and karyopherin-beta. LEDGF residues essential for the interaction with IN were localized to interhelical loop regions of the bundle structure. Interaction-defective IN mutants were previously shown to cripple replication although they retained catalytic function. The initial structure determination of a host cell factor that tightly binds to a retroviral enzyme lays the groundwork for understanding enzyme-host interactions important for viral replication.
Cherepanov
Peter
P
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA.
Sun
Zhen-Yu J
ZY
Rahman
Shaila
S
Maertens
Goedele
G
Wagner
Gerhard
G
Engelman
Alan
A
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D003001:Cloning, Molecular; D005346:Fibroblast Growth Factors; D006133:Growth Substances / Q000737:chemistry* / Q000378:metabolism*; D019427:HIV Integrase / Q000737:chemistry* / Q000378:metabolism*; D015497:HIV-1 / Q000201:enzymology*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008322:Mammals; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016296:Mutagenesis; D016366:Open Reading Frames; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D015183:Restriction Mapping
D006133:Growth Substances; D011994:Recombinant Proteins; C039825:eye-derived growth factor; D005346:Fibroblast Growth Factors; D019427:HIV Integrase