Higher nucleoporin-Importinβ affinity at the nuclear basket increases nucleocytoplasmic import.

Several in vitro studies have shown the presence of an affinity gradient in nuclear pore complex proteins for the import receptor Importinβ, at least partially contributing to nucleocytoplasmic transport, while others have historically argued against the presence of such a gradient. Nonetheless, the...

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Autores principales:	Mohammad Azimi, Mohammad R K Mofrad
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/cb92e89e32a1406a8787f38e05f59d1f
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spelling	oai:doaj.org-article:cb92e89e32a1406a8787f38e05f59d1f2021-11-18T08:44:46ZHigher nucleoporin-Importinβ affinity at the nuclear basket increases nucleocytoplasmic import.1932-620310.1371/journal.pone.0081741https://doaj.org/article/cb92e89e32a1406a8787f38e05f59d1f2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24282617/?tool=EBIhttps://doaj.org/toc/1932-6203Several in vitro studies have shown the presence of an affinity gradient in nuclear pore complex proteins for the import receptor Importinβ, at least partially contributing to nucleocytoplasmic transport, while others have historically argued against the presence of such a gradient. Nonetheless, the existence of an affinity gradient has remained an uncharacterized contributing factor. To shed light on the affinity gradient theory and better characterize how the existence of such an affinity gradient between the nuclear pore and the import receptor may influence the nucleocytoplasmic traffic, we have developed a general-purpose agent based modeling (ABM) framework that features a new method for relating rate constants to molecular binding and unbinding probabilities, and used our ABM approach to quantify the effects of a wide range of forward and reverse nucleoporin-Importinβ affinity gradients. Our results indicate that transport through the nuclear pore complex is maximized with an effective macroscopic affinity gradient of 2000 µM, 200 µM and 10 µM in the cytoplasmic, central channel and nuclear basket respectively. The transport rate at this gradient is approximately 10% higher than the transport rate for a comparable pore lacking any affinity gradient, which has a peak transport rate when all nucleoporins have an affinity of 200 µM for Importinβ. Furthermore, this optimal ratio of affinity gradients is representative of the ratio of affinities reported for the yeast nuclear pore complex--suggesting that the affinity gradient seen in vitro is highly optimized.Mohammad AzimiMohammad R K MofradPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 11, p e81741 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Mohammad Azimi Mohammad R K Mofrad Higher nucleoporin-Importinβ affinity at the nuclear basket increases nucleocytoplasmic import.
description	Several in vitro studies have shown the presence of an affinity gradient in nuclear pore complex proteins for the import receptor Importinβ, at least partially contributing to nucleocytoplasmic transport, while others have historically argued against the presence of such a gradient. Nonetheless, the existence of an affinity gradient has remained an uncharacterized contributing factor. To shed light on the affinity gradient theory and better characterize how the existence of such an affinity gradient between the nuclear pore and the import receptor may influence the nucleocytoplasmic traffic, we have developed a general-purpose agent based modeling (ABM) framework that features a new method for relating rate constants to molecular binding and unbinding probabilities, and used our ABM approach to quantify the effects of a wide range of forward and reverse nucleoporin-Importinβ affinity gradients. Our results indicate that transport through the nuclear pore complex is maximized with an effective macroscopic affinity gradient of 2000 µM, 200 µM and 10 µM in the cytoplasmic, central channel and nuclear basket respectively. The transport rate at this gradient is approximately 10% higher than the transport rate for a comparable pore lacking any affinity gradient, which has a peak transport rate when all nucleoporins have an affinity of 200 µM for Importinβ. Furthermore, this optimal ratio of affinity gradients is representative of the ratio of affinities reported for the yeast nuclear pore complex--suggesting that the affinity gradient seen in vitro is highly optimized.
format	article
author	Mohammad Azimi Mohammad R K Mofrad
author_facet	Mohammad Azimi Mohammad R K Mofrad
author_sort	Mohammad Azimi
title	Higher nucleoporin-Importinβ affinity at the nuclear basket increases nucleocytoplasmic import.
title_short	Higher nucleoporin-Importinβ affinity at the nuclear basket increases nucleocytoplasmic import.
title_full	Higher nucleoporin-Importinβ affinity at the nuclear basket increases nucleocytoplasmic import.
title_fullStr	Higher nucleoporin-Importinβ affinity at the nuclear basket increases nucleocytoplasmic import.
title_full_unstemmed	Higher nucleoporin-Importinβ affinity at the nuclear basket increases nucleocytoplasmic import.
title_sort	higher nucleoporin-importinβ affinity at the nuclear basket increases nucleocytoplasmic import.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/cb92e89e32a1406a8787f38e05f59d1f
work_keys_str_mv	AT mohammadazimi highernucleoporinimportinbaffinityatthenuclearbasketincreasesnucleocytoplasmicimport AT mohammadrkmofrad highernucleoporinimportinbaffinityatthenuclearbasketincreasesnucleocytoplasmicimport
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Higher nucleoporin-Importinβ affinity at the nuclear basket increases nucleocytoplasmic import.

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