Insights into the Structural Dynamics of Nucleocytoplasmic Transport of tRNA by Exportin-t

Gupta, Asmita and Kailasam, Senthilkumar and Bansal, Manju (2016) Insights into the Structural Dynamics of Nucleocytoplasmic Transport of tRNA by Exportin-t. In: BIOPHYSICAL JOURNAL, 110 (6). pp. 1264-1279.

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Abstract

Exportin-t (Xpot) transports mature 5'- and 3'-end processed tRNA from the nucleus to the cytoplasm by associating with a small G-protein Ran (RAs-related nuclear protein), in the nucleus. The release of tRNA in cytoplasm involves RanGTP hydrolysis. Despite the availability of crystal structures of nuclear and cytosolic forms of Xpot, the molecular details regarding the sequential events leading to tRNA release and subsequent conformational changes occurring in Xpot remain unknown. We have performed a combination of classical all-atom and accelerated molecular dynamics simulations on a set of complexes involving Xpot to study a range of features including conformational flexibility of free and cargo-bound Xpot and functionally critical contacts between Xpot and its cargo. The systems investigated include free Xpot and its different complexes, bound either to Ran (GTP/GDP) or tRNA or both. This approach provided a statistically reliable estimate of structural dynamics of Xpot after cargo release. The mechanistic basis for Xpot opening after cargo release has been explained in terms of dynamic structural hinges, about which neighboring region could be displaced to facilitate the nuclear to cytosolic state transition. Post-RanGTP hydrolysis, a cascade of events including local conformational change in RanGTP and loss of critical contacts at Xpot/tRNA interface suggest factors responsible for eventual release of tRNA. The level of flexibility in different Xpot complexes varied depending on the arrangement of individual HEAT repeats. Current study provides one of the most comprehensive and robust analysis carried out on this protein using molecular dynamics schemes.

Item Type:	Journal Article
Publication:	BIOPHYSICAL JOURNAL
Publisher:	CELL PRESS
Additional Information:	Copy right for this article belongs to the CELL PRESS, 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
Department/Centre:	Division of Biological Sciences > Molecular Biophysics Unit
Date Deposited:	11 May 2016 07:28
Last Modified:	11 May 2016 07:28
URI:	http://eprints.iisc.ac.in/id/eprint/53789

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