4KNH

Structure of the Chaetomium thermophilum adaptor nucleoporin Nup192 N-terminal domain

4KNH の概要

• エントリーDOI: 10.2210/pdb4knh/pdb
• 分子名称: Nup192p, SULFATE ION, 1,2-ETHANEDIOL, ... (5 entities in total)
• 機能のキーワード: heat repeat protein, arm repeat protein, nuclear pore complex, transport protein
• 由来する生物種: Chaetomium thermophilum var. thermophilum
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 219705.05

構造登録者

Stuwe, T.,Lin, D.H.,Collins, L.N.,Hoelz, A. (登録日: 2013-05-09, 公開日: 2014-02-05, 最終更新日: 2024-02-28)

主引用文献

Stuwe, T.,Lin, D.H.,Collins, L.N.,Hurt, E.,Hoelz, A.
Evidence for an evolutionary relationship between the large adaptor nucleoporin Nup192 and karyopherins.
Proc.Natl.Acad.Sci.USA, 111:2530-2535, 2014

PubMed Abstract: Nucleocytoplasmic 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 ∼110-kDa N-terminal domain (NTD) of Nup192 at 2.7-Å 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-α (Kap-α) and β-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-α 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.

PubMed: 24505056
DOI: 10.1073/pnas.1311081111

実験手法

X-RAY DIFFRACTION (2.702 Å)