5b56

Crystal structure of HIV-1 VPR C-Terminal domain and DIBB-M-Importin-Alpha2 complex

spinqualitylabelsall models 5b56, resolution 2.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5b56 is a 6 chain structure with sequence from Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Related: 3wpt Gene: Kpna2 (LK3 transgenic mice) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [IMA1_MOUSE] Functions in nuclear protein import as an adapter protein for nuclear receptor KPNB1. Binds specifically and directly to substrates containing either a simple or bipartite NLS motif. Docking of the importin/substrate complex to the nuclear pore complex (NPC) is mediated by KPNB1 through binding to nucleoporin FxFG repeats and the complex is subsequently translocated through the pore by an energy requiring, Ran-dependent mechanism. At the nucleoplasmic side of the NPC, Ran binds to importin-beta and the three components separate and importin-alpha and -beta are re-exported from the nucleus to the cytoplasm where GTP hydrolysis releases Ran from importin. The directionality of nuclear import is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus. [VPR_HV1B9] Involved in the transport of the viral pre-integration (PIC) complex to the nucleus during the early stages of the infection. This function is crucial for viral infection of non-dividing macrophages. May interact with karyopherin alpha/KPNA1 and KPNA2 to increase their affinity for proteins containing basic-type nuclear localization signal, including the viral matrix protein MA, thus facilitating the translocation of the viral genome into the nucleus. May also act directly at the nuclear pore complex, by binding nucleoporins phenylalanine-glycine (FG)-repeat regions (By similarity). May target specific host proteins for degradation by the 26S proteasome. Acts by associating with the cellular CUL4A-DDB1 E3 ligase complex through direct interaction with host VPRPB/DCAF-1. This change in the E3 ligase substrate specificity would result in cell cycle arrest or apoptosis in infected cells. Prevents infected cells from undergoing mitosis and proliferating, by inducing arrest or delay in the G2 phase of the cell cycle. This arrest creates a favorable environment for maximizing viral expression and production by rendering the HIV-1 LTR transcriptionally more active. In this context, Vpr stimulates gene expression driven by the HIV-1 LTR by interacting with human SP1, TFIIB and TFIID. Cell cycle arrest reportedly occurs within hours of infection and is not blocked by antiviral agents, suggesting that it is initiated by the Vpr carried into the virion. Additionally, Vpr induces apoptosis in a cell cycle dependent manner suggesting that these two effects are mechanistically linked. Interacts with mitochondrial permeability transition pore complex (PTPC). This interaction induces a rapid dissipation of the mitochondrial transmembrane potential, and mitochondrial release of apoptogenic proteins such as cytochrome C or apoptosis inducing factors. Detected in the serum and cerebrospinal fluid of AIDS patient, Vpr may also induce cell death to bystander cells (By similarity). Publication Abstract from PubMed Viral protein R (Vpr) is an accessory gene product of human immunodeficiency virus type 1 (HIV-1) that plays multiple important roles associated with viral replication. Structural studies using NMR have revealed that Vpr consists of three alpha-helices and contains flexible N- and C-termini. However, the molecular mechanisms associated with Vpr function have not been elucidated. To investigate Vpr multifunctionality, we performed an X-ray crystallographic study of Vpr complexes containing importin-alpha, a known Vpr binding partner present in host cells. Elucidation of the crystal structure revealed that the flexible C-terminus changes its conformation to a twisted beta-turn via an induced-fit mechanism, enabling binding to a minor nuclear localization signal (NLS) site of importin-alpha. The Vpr C-terminus can also bind with major NLS sites of importin-alpha in an extended conformation in different ways. These results, which represent the first reported crystallographic analysis of Vpr, demonstrate the multifunctional aspects that enable Vpr interaction with a variety of cellular proteins. Molecular Mechanism of HIV-1 Vpr for Binding to Importin-alpha.,Miyatake H, Sanjoh A, Murakami T, Murakami H, Matsuda G, Hagiwara K, Yokoyama M, Sato H, Miyamoto Y, Dohmae N, Aida Y J Mol Biol. 2016 May 12. pii: S0022-2836(16)30140-1. doi:, 10.1016/j.jmb.2016.05.003. PMID:27181198 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Importin 3D structures Vpr protein

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