Structure-function mapping of a heptameric module in the nuclear pore complex.

Structure-function mapping of a heptameric module in the nuclear pore complex.
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DOI:
10.1083/jcb.201109008
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发表时间:
2012-02-20
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Rout MP
Rout MP
中科院分区:
其他
文献类型:
--
作者:
Fernandez-Martinez J;Phillips J;Sekedat MD;Diaz-Avalos R;Velazquez-Muriel J;Franke JD;Williams R;Stokes DL;Chait BT;Sali A;Rout MP

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Integration of EM, protein–protein interaction, and phenotypic data reveals novel insights into the structure and function of the nuclear pore complex’s ∼600-kD heptameric Nup84 complex. The nuclear pore complex (NPC) is a multiprotein assembly that serves as the sole mediator of nucleocytoplasmic exchange in eukaryotic cells. In this paper, we use an integrative approach to determine the structure of an essential component of the yeast NPC, the ∼600-kD heptameric Nup84 complex, to a precision of ∼1.5 nm. The configuration of the subunit structures was determined by satisfaction of spatial restraints derived from a diverse set of negative-stain electron microscopy and protein domain–mapping data. Phenotypic data were mapped onto the complex, allowing us to identify regions that stabilize the NPC’s interaction with the nuclear envelope membrane and connect the complex to the rest of the NPC. Our data allow us to suggest how the Nup84 complex is assembled into the NPC and propose a scenario for the evolution of the Nup84 complex through a series of gene duplication and loss events. This work demonstrates that integrative approaches based on low-resolution data of sufficient quality can generate functionally informative structures at intermediate resolution.
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