Imperial College London
Alternate

DrGoedeleMaertens

Faculty of Medicine, Department of Infectious Disease

Reader in Molecular Virology
 
 
 
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Contact

 

+44 (0)20 7594 3655g.maertens Website

 
 
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Location

 

314, Medical School BuildingNorfolk PlaceSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Maertens:2014:10.1073/pnas.1320755111,
author = {Maertens, GN and Cook, NJ and Wang, W and Hare, S and Gupta, SS and Oeztop, I and Lee, K and Pye, VE and Cosnefroy, O and Snijders, AP and KewalRamani, VN and Fassati, A and Engelman, A and Cherepanov, P},
doi = {10.1073/pnas.1320755111},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
pages = {2728--2733},
title = {Structural basis for nuclear import of splicing factors by human transportin 3},
url = {http://dx.doi.org/10.1073/pnas.1320755111},
volume = {111},
year = {2014}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Transportin 3 (Tnpo3, Transportin-SR2) is implicated in nuclear import of splicing factors and HIV-1 replication. Herein, we show that the majority of cellular Tnpo3 binding partners contain arginine-serine (RS) repeat domains and present crystal structures of human Tnpo3 in its free as well as GTPase Ran- and alternative splicing factor/splicing factor 2 (ASF/SF2)-bound forms. The flexible β-karyopherin fold of Tnpo3 embraces the RNA recognition motif and RS domains of the cargo. A constellation of charged residues on and around the arginine-rich helix of Tnpo3 HEAT repeat 15 engage the phosphorylated RS domain and are critical for the recognition and nuclear import of ASF/SF2. Mutations in the same region of Tnpo3 impair its interaction with the cleavage and polyadenylation specificity factor 6 (CPSF6) and its ability to support HIV-1 replication. Steric incompatibility of the RS domain and RanGTP engagement by Tnpo3 provides the mechanism for cargo release in the nucleus. Our results elucidate the structural bases for nuclear import of splicing factors and the Tnpo3–CPSF6 nexus in HIV-1 biology.
AU  - Maertens,GN
AU  - Cook,NJ
AU  - Wang,W
AU  - Hare,S
AU  - Gupta,SS
AU  - Oeztop,I
AU  - Lee,K
AU  - Pye,VE
AU  - Cosnefroy,O
AU  - Snijders,AP
AU  - KewalRamani,VN
AU  - Fassati,A
AU  - Engelman,A
AU  - Cherepanov,P
DO  - 10.1073/pnas.1320755111
EP  - 2733
PY  - 2014///
SN  - 0027-8424
SP  - 2728
TI  - Structural basis for nuclear import of splicing factors by human transportin 3
T2  - Proceedings of the National Academy of Sciences of the United States of America
UR  - http://dx.doi.org/10.1073/pnas.1320755111
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000331396500067&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://www.pnas.org/content/111/7/2728/
VL  - 111
ER  -
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