Structure of the exportin Xpo4 in complex with RanGTP and the hypusine-containing translation factor eIF5A.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 27306458.
- Also identified by DOI 10.1038/ncomms11952 and PMC identifier 4912631.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
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.
Medical subject headings
- Karyopherins
- Lysine
- Peptide Initiation Factors
- RNA-Binding Proteins
- ran GTP-Binding Protein