1z9e
From Proteopedia
Solution structure of the HIV-1 integrase-binding domain in LEDGF/p75
Structural highlights
DiseasePSIP1_HUMAN Note=A chromosomal aberration involving PSIP1 is associated with pediatric acute myeloid leukemia (AML) with intermediate characteristics between M2-M3 French-American-British (FAB) subtypes. Translocation t(9;11)(p22;p15) with NUP98. The chimeric transcript is an in-frame fusion of NUP98 exon 8 to PSIP1/LEDGF exon 4. FunctionPSIP1_HUMAN Transcriptional coactivator involved in neuroepithelial stem cell differentiation and neurogenesis. Involved in particular in lens epithelial cell gene regulation and stress responses. May play an important role in lens epithelial to fiber cell terminal differentiation. May play a protective role during stress-induced apoptosis. Isoform 2 is a more general and stronger transcriptional coactivator. Isoform 2 may also act as an adapter to coordinate pre-mRNA splicing. Cellular cofactor for lentiviral integration.[1] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedLens 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. Solution structure of the HIV-1 integrase-binding domain in LEDGF/p75.,Cherepanov P, Sun ZY, Rahman S, Maertens G, Wagner G, Engelman A Nat Struct Mol Biol. 2005 Jun;12(6):526-32. Epub 2005 May 15. PMID:15895093[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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