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Crystal structure of HIV-1 capsid N-terminal domain in complex with NUP358 cyclophilinCrystal structure of HIV-1 capsid N-terminal domain in complex with NUP358 cyclophilin
Structural highlights
DiseaseRBP2_HUMAN Defects in RANBP2 are the cause of encephalopathy acute infection-induced type 3 (IIAE3) [MIM:608033. A rapidly progressive encephalopathy manifesting in susceptibile individuals with seizures and coma. It can occur within days in otherwise healthy children after common viral infections such as influenza and parainfluenza, without evidence of viral infection of the brain or inflammatory cell infiltration. Brain T2-weighted magnetic resonance imaging reveals characteristic symmetric lesions present in the thalami, pons and brainstem. Note=Mutations in the RANBP2 gene predispose to IIAE3, but by themselves are insufficient to make the phenotype fully penetrant; additional genetic and environmental factors are required (PubMed:19118815).[1] FunctionRBP2_HUMAN E3 SUMO-protein ligase which facilitates SUMO1 and SUMO2 conjugation by UBE2I. Involved in transport factor (Ran-GTP, karyopherin)-mediated protein import via the F-G repeat-containing domain which acts as a docking site for substrates. Could also have isomerase or chaperone activity and may bind RNA or DNA. Component of the nuclear export pathway. Specific docking site for the nuclear export factor exportin-1.[2] [3] [4] [5] Publication Abstract from PubMedBACKGROUND: Lentiviruses such as HIV-1 can be distinguished from other retroviruses by the cyclophilin A-binding loop in their capsid and their ability to infect non-dividing cells. Infection of non-dividing cells requires transport through the nuclear pore but how this is mediated is unknown. RESULTS: Here we present the crystal structure of the N-terminal capsid domain of HIV-1 in complex with the cyclophilin domain of nuclear pore protein NUP358. The structure reveals that HIV-1 is positioned to allow single-bond resonance stabilisation of exposed capsid residue P90. NMR exchange experiments demonstrate that NUP358 is an active isomerase, which efficiently catalyzes cis-trans isomerization of the HIV-1 capsid. In contrast, the distantly related feline lentivirus FIV can bind NUP358 but is neither isomerized by it nor requires it for infection. CONCLUSION: Isomerization by NUP358 may be preserved by HIV-1 to target the nuclear pore and synchronize nuclear entry with capsid uncoating. HIV-1 capsid undergoes coupled binding and isomerization by the nuclear pore protein NUP358.,Bichel K, Price AJ, Schaller T, Towers GJ, Freund SM, James LC Retrovirology. 2013 Jul 31;10(1):81. doi: 10.1186/1742-4690-10-81. PMID:23902822[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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