Journal Article

Structure of the exportin Xpo4 in complex with RanGTP and the hypusine-containing translation factor eIF5A

Aksu, Metin, Görlich, Dirk, Trakhanov, Sergei

2016

Overview

Xpo4 is a bidirectional nuclear transport receptor that mediates nuclear export of eIF5A and Smad3 as well as import of Sox2 and SRY. How Xpo4 recognizes such a variety of cargoes is as yet unknown. Here we present the crystal structure of the RanGTP·Xpo4·eIF5A export complex at 3.2 Å resolution. Xpo4 has a similar structure as CRM1, but the NES-binding site is occluded, and a new interaction site evolved that recognizes both globular domains of eIF5A. eIF5A contains hypusine, a unique amino acid with two positive charges, which is essential for cell viability and eIF5A function in translation. The hypusine docks into a deep, acidic pocket of Xpo4 and is thus a critical element of eIF5A’s complex export signature. This further suggests that Xpo4 recognizes other cargoes differently, and illustrates how Xpo4 suppresses – in a chaperone-like manner – undesired interactions of eIF5A inside nuclei. Xpo4 imports Sox2 and other proteins into the cell nucleus, while exporting eIF5A or Smad3; how it recognizes these proteins has been unclear. Here, the authors solved the crystal structure of the RanGTP, Xpo4 and eIF5A complex and investigate how Xpo4 identifies its major export cargo.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 14/19 / 14/34 / 38/22 / 38/23 / 631/45/535 / 631/45/612/1222 / 82/16 / 82/29 / 82/80 / 82/83 / 96/63 / Amino Acid Sequence / Amino acids / Binding Sites / Cloning, Molecular / Crystallography, X-Ray / Cytoplasm / Docks / Escherichia coli - genetics / Escherichia coli - metabolism / Eukaryotic Translation Initiation Factor 5A / Gene Expression / Genetic Vectors - chemistry / Genetic Vectors - metabolism / Humanities and Social Sciences / Humans / Karyopherins - chemistry / Karyopherins - genetics / Karyopherins - metabolism / Kinetics / Lysine - analogs & derivatives / Lysine - chemistry / Lysine - metabolism / Molecular Docking Simulation / multidisciplinary / Peptide Initiation Factors - chemistry / Peptide Initiation Factors - genetics / Peptide Initiation Factors - metabolism / Protein Binding / Protein Conformation, alpha-Helical / Protein Conformation, beta-Strand / Protein Interaction Domains and Motifs / Proteins / ran GTP-Binding Protein - chemistry / ran GTP-Binding Protein - genetics / ran GTP-Binding Protein - metabolism / Recombinant Proteins - chemistry / Recombinant Proteins - genetics / Recombinant Proteins - metabolism / RNA-Binding Proteins - chemistry / RNA-Binding Proteins - genetics / RNA-Binding Proteins - metabolism / Science / Science (multidisciplinary) / Sequence Alignment / Sequence Homology, Amino Acid / Thermodynamics / Transfer RNA