4i9y
Structure of the C-terminal domain of Nup358
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 PubMedThe nuclear pore complex is the sole mediator of bidirectional transport between the nucleus and cytoplasm. Nup358 is a metazoan-specific nucleoporin that localizes to the cytoplasmic filaments and provides several binding sites for the mobile nucleocytoplasmic transport machinery. Here we present the crystal structure of the C-terminal domain (CTD) of Nup358 at 1.75A resolution. The structure reveals that the CTD adopts a cyclophilin-like fold with a non-canonical active-site configuration. We determined biochemically that the CTD possesses weak peptidyl-prolyl isomerase activity and show that the active-site cavity mediates a weak association with the human immunodeficiency virus-1 capsid protein, supporting its role in viral infection. Overall, the surface is evolutionarily conserved, suggesting that the CTD serves as a protein-protein interaction platform. However, we demonstrate that the CTD is dispensable for nuclear envelope localization of Nup358, suggesting that the CTD does not interact with other nucleoporins. Structural and Functional Analysis of the C-Terminal Domain of Nup358/RanBP2.,Lin DH, Zimmermann S, Stuwe T, Stuwe E, Hoelz A J Mol Biol. 2013 Jan 23. pii: S0022-2836(13)00037-5. doi:, 10.1016/j.jmb.2013.01.021. PMID:23353830[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||||||
