4knh
From Proteopedia
Structure of the Chaetomium thermophilum adaptor nucleoporin Nup192 N-terminal domain
Structural highlights
FunctionNU192_CHATD Functions as a component of the nuclear pore complex (NPC). NPC components, collectively referred to as nucleoporins (NUPs), can play the role of both NPC structural components and of docking or interaction partners for transiently associated nuclear transport factors. NUP192 is located to the NPC core at the nuclear membrane and is essential for de novo assembly of NPCs.[UniProtKB:P47054] Publication Abstract from PubMedNucleocytoplasmic transport is facilitated by nuclear pore complexes (NPCs), which are massive proteinaceous transport channels embedded in the nuclear envelope. Nup192 is a major component of an adaptor nucleoporin subcomplex proposed to link the NPC coat with the central transport channel. Here, we present the structure of the approximately 110-kDa N-terminal domain (NTD) of Nup192 at 2.7-A resolution. The structure reveals an open ring-shaped architecture composed of Huntingtin, EF3, PP2A, and TOR1 (HEAT) and Armadillo (ARM) repeats. A comparison of different conformations indicates that the NTD consists of two rigid halves connected by a flexible hinge. Unexpectedly, the two halves of the ring are structurally related to karyopherin-alpha (Kap-alpha) and beta-karyopherin family members. Biochemically, we identify a conserved patch that binds an unstructured segment in Nup53 and show that a C-terminal tail region binds to a putative helical fragment in Nic96. The Nup53 segment that binds Nup192 is a classical nuclear localization-like sequence that interacts with Kap-alpha in a mutually exclusive and mechanistically distinct manner. The disruption of the Nup53 and Nic96 binding sites in vivo yields growth and mRNA export defects, revealing their critical role in proper NPC function. Surprisingly, both interactions are dispensable for NPC localization, suggesting that Nup192 possesses another nucleoporin interaction partner. These data indicate that the structured domains in the adaptor nucleoporin complex are held together by peptide interactions that resemble those found in karyopherin*cargo complexes and support the proposal that the adaptor nucleoporins arose from ancestral karyopherins. Evidence for an evolutionary relationship between the large adaptor nucleoporin Nup192 and karyopherins.,Stuwe T, Lin DH, Collins LN, Hurt E, Hoelz A Proc Natl Acad Sci U S A. 2014 Feb 18;111(7):2530-5. doi:, 10.1073/pnas.1311081111. Epub 2014 Feb 6. PMID:24505056[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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