title: Solution structure of the HIV-1 integrase-binding domain in LEDGF/p75.
abstract: 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.
authors.affiliation: Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Cherepanov
authors.forename: Zhen-Yu J
authors.initials: ZY
authors.lastname: Sun
authors.forename: Shaila
authors.initials: S
authors.lastname: Rahman
authors.forename: Goedele
authors.initials: G
authors.lastname: Maertens
authors.forename: Gerhard
authors.initials: G
authors.lastname: Wagner
authors.forename: Alan
authors.initials: A
authors.lastname: Engelman
mesh_terms: 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
chemical_list: D006133:Growth Substances; D011994:Recombinant Proteins; C039825:eye-derived growth factor; D005346:Fibroblast Growth Factors; D019427:HIV Integrase