Cargando…
Structure of the exportin Xpo4 in complex with RanGTP and the hypusine-containing translation factor eIF5A
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. Xp...
Autores principales: | , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4912631/ https://www.ncbi.nlm.nih.gov/pubmed/27306458 http://dx.doi.org/10.1038/ncomms11952 |
_version_ | 1782438291055837184 |
---|---|
author | Aksu, Metin Trakhanov, Sergei Görlich, Dirk |
author_facet | Aksu, Metin Trakhanov, Sergei Görlich, Dirk |
author_sort | Aksu, Metin |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4912631 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-49126312016-06-29 Structure of the exportin Xpo4 in complex with RanGTP and the hypusine-containing translation factor eIF5A Aksu, Metin Trakhanov, Sergei Görlich, Dirk Nat Commun Article 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. Nature Publishing Group 2016-06-16 /pmc/articles/PMC4912631/ /pubmed/27306458 http://dx.doi.org/10.1038/ncomms11952 Text en Copyright © 2016, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Aksu, Metin Trakhanov, Sergei Görlich, Dirk Structure of the exportin Xpo4 in complex with RanGTP and the hypusine-containing translation factor eIF5A |
title | Structure of the exportin Xpo4 in complex with RanGTP and the hypusine-containing translation factor eIF5A |
title_full | Structure of the exportin Xpo4 in complex with RanGTP and the hypusine-containing translation factor eIF5A |
title_fullStr | Structure of the exportin Xpo4 in complex with RanGTP and the hypusine-containing translation factor eIF5A |
title_full_unstemmed | Structure of the exportin Xpo4 in complex with RanGTP and the hypusine-containing translation factor eIF5A |
title_short | Structure of the exportin Xpo4 in complex with RanGTP and the hypusine-containing translation factor eIF5A |
title_sort | structure of the exportin xpo4 in complex with rangtp and the hypusine-containing translation factor eif5a |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4912631/ https://www.ncbi.nlm.nih.gov/pubmed/27306458 http://dx.doi.org/10.1038/ncomms11952 |
work_keys_str_mv | AT aksumetin structureoftheexportinxpo4incomplexwithrangtpandthehypusinecontainingtranslationfactoreif5a AT trakhanovsergei structureoftheexportinxpo4incomplexwithrangtpandthehypusinecontainingtranslationfactoreif5a AT gorlichdirk structureoftheexportinxpo4incomplexwithrangtpandthehypusinecontainingtranslationfactoreif5a |