3dcg
From Proteopedia
Crystal Structure of the HIV Vif BC-box in Complex with Human ElonginB and ElonginC
Structural highlights
Function[ELOB_HUMAN] SIII, also known as elongin, is a general transcription elongation factor that increases the RNA polymerase II transcription elongation past template-encoded arresting sites. Subunit A is transcriptionally active and its transcription activity is strongly enhanced by binding to the dimeric complex of the SIII regulatory subunits B and C (elongin BC complex).[1] [2] The elongin BC complex seems to be involved as an adapter protein in the proteasomal degradation of target proteins via different E3 ubiquitin ligase complexes, including the von Hippel-Lindau ubiquitination complex CBC(VHL). By binding to BC-box motifs it seems to link target recruitment subunits, like VHL and members of the SOCS box family, to Cullin/RBX1 modules that activate E2 ubiquitination enzymes.[3] [4] [VIF_HV1N5] Counteracts the innate antiviral activity of human APOBEC3F and APOBEC3G. Forms a complex with host APOBEC3F and APOBEC3G thus preventing the entry of these lethally hypermutating enzymes into progeny virions. Recruits an active E3 ubiquitin ligase complex composed of elongin BC, CUL5, and RBX2 to induce polyubiquitination of APOBEC3G and APOBEC3F. In turn, they are directed to the 26S proteasome for degradation. Vif interaction with APOBEC3G also blocks its cytidine deaminase activity in a proteasome-independent manner, suggesting a dual inhibitory mechanism. May interact directly with APOBEC3G mRNA in order to inhibit its translation. Seems to play a role in viral morphology by affecting the stability of the viral nucleoprotein core. Finally, Vif also contributes to the G2 cell cycle arrest observed in HIV infected cells (By similarity).[5] [6] [ELOC_HUMAN] SIII, also known as elongin, is a general transcription elongation factor that increases the RNA polymerase II transcription elongation past template-encoded arresting sites. Subunit A is transcriptionally active and its transcription activity is strongly enhanced by binding to the dimeric complex of the SIII regulatory subunits B and C (elongin BC complex).[7] The elongin BC complex seems to be involved as an adapter protein in the proteasomal degradation of target proteins via different E3 ubiquitin ligase complexes, including the von Hippel-Lindau ubiquitination complex CBC(VHL). By binding to BC-box motifs it seems to link target recruitment subunits, like VHL and members of the SOCS box family, to Cullin/RBX1 modules that activate E2 ubiquitination enzymes.[8] 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 PubMedHuman immunodeficiency virus (HIV) virion infectivity factor (Vif) causes the proteasome-mediated destruction of human antiviral protein APOBEC3G by tethering it to a cellular E3 ubiquitin ligase composed of ElonginB, ElonginC, Cullin5, and Rbx2. It has been proposed that HIV Vif hijacks the E3 ligase through two regions within its C-terminal domain: a BC box region that interacts with ElonginC and a novel zinc finger motif that interacts with Cullin5. We have determined the crystal structure of the HIV Vif BC box in complex with human ElonginB and ElonginC. This complex presents direct structural evidence of the recruitment of a human ubiquitin ligase by a viral BC box protein that mimics the conserved interactions of cellular ubiquitin ligases. We further mutated conserved hydrophobic residues in a region downstream of the Vif BC box. These mutations demonstrate that this region, the Vif Cullin box, composes a third E3-ligase recruiting site critical for interaction between Vif and Cullin5. Furthermore, our homology modeling reveals that the Vif Cullin box and zinc finger motif may be positioned adjacent to the N terminus of Cullin5 for interaction with loop regions in the first cullin repeat of Cullin5. Structural insight into the human immunodeficiency virus Vif SOCS box and its role in human E3 ubiquitin ligase assembly.,Stanley BJ, Ehrlich ES, Short L, Yu Y, Xiao Z, Yu XF, Xiong Y J Virol. 2008 Sep;82(17):8656-63. Epub 2008 Jun 18. PMID:18562529[9] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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Categories: Homo sapiens | Viruses | Ehrlich, E S | Short, L | Stanley, B J | Xiao, Z | Xiong, Y | Yu, X F | Yu, Y | Aid | Hiv | Host-virus interaction | Ligase-viral protein complex | Membrane | Nucleus | Phosphoprotein | Rna-binding | Transcription | Transcription regulation | Ubl conjugation pathway | Vif | Virion
