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Structural basis for importin alpha 3 specificity of W proteins in Hendra and Nipah viruses.


ABSTRACT: Seven human isoforms of importin ? mediate nuclear import of cargo in a tissue- and isoform-specific manner. How nuclear import adaptors differentially interact with cargo harbouring the same nuclear localisation signal (NLS) remains poorly understood, as the NLS recognition region is highly conserved. Here, we provide a structural basis for the nuclear import specificity of W proteins in Hendra and Nipah viruses. We determine the structural interfaces of these cargo bound to importin ?1 and ?3, identifying a 2.4-fold more extensive interface and >?50-fold higher binding affinity for importin ?3. Through the design of importin ?1 and ?3 chimeric and mutant proteins, together with structures of cargo-free importin ?1 and ?3 isoforms, we establish that the molecular basis of specificity resides in the differential positioning of the armadillo repeats 7 and 8. Overall, our study provides mechanistic insights into a range of important nucleocytoplasmic transport processes reliant on isoform adaptor specificity.

SUBMITTER: Smith KM 

PROVIDER: S-EPMC6135763 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Structural basis for importin alpha 3 specificity of W proteins in Hendra and Nipah viruses.

Smith Kate M KM   Tsimbalyuk Sofiya S   Edwards Megan R MR   Cross Emily M EM   Batra Jyoti J   Soares da Costa Tatiana P TP   Aragão David D   Basler Christopher F CF   Forwood Jade K JK  

Nature communications 20180912 1


Seven human isoforms of importin α mediate nuclear import of cargo in a tissue- and isoform-specific manner. How nuclear import adaptors differentially interact with cargo harbouring the same nuclear localisation signal (NLS) remains poorly understood, as the NLS recognition region is highly conserved. Here, we provide a structural basis for the nuclear import specificity of W proteins in Hendra and Nipah viruses. We determine the structural interfaces of these cargo bound to importin α1 and α3,  ...[more]

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