Westlake News ACADEMICS

Yigong Shi’s Lab Reports Cryo-EM Structure of Nuclear Ring from Nuclear Pore Complex

16, 2022

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The nuclei of eukaryotes are enclosed by double-membrane envelopes. The nuclear envelopes (NEs) reduce mutual interference between the biochemical reactions taking place in the nucleus and the cytoplasm, respectively; however, they also restrict the free exchange of substances between the nucleus and the cytoplasm. The nuclear pore complex (NPC) is the only route for cargo transport on the NE. Besides, the NPC also plays an important role in the regulation of gene expression. Malfunctioning of the NPC leads to multiple diseases including cancer. A high-resolution structure of the NPC facilitates the understanding of the basic processes of life and the mechanism underlying diseases, which may further inspire the development of relative therapies or drugs.

The NPC is one of the largest and most complicated macro-molecules in the eukaryotic cell. A vertebrate NPC has a molecular mass of over 100 megadaltons (MDa) and consists of cytoplasmic filaments (CF), a cytoplasmic ring (CR), an inner ring (IR), a nuclear ring (NR), a nuclear basket (NB), and a luminal ring (LR). Structural elucidation of the NPC is always regarded as one of the two holy grails in structural biology.

Recently, the Yigong Shi lab at Westlake University published an article online on Cell Research (https://www.nature.com/articles/s41422-021-00610-w) titled "Cryo-EM structure of the nuclear ring from Xenopus laevis nuclear pore complex". In this article, they reported the single-particle cryo-EM structure of the NR subunit from Xenopus laevis NPC with the highest resolution (5.6 Å) to date.

In their structural model, the NR subunit comprises two 10-membered Y complexes, each with the nucleoporin ELYS closely associating with Nup160 and Nup37 of the long arm. Unlike the CR or IR, the NR subunit contains only one molecule each of Nup205 and Nup93. Nup205 binds both arms of the Y complexes and interacts with the stem of inner Y complex from the neighboring subunit. Nup93 connects the stems of inner and outer Y complexes within the same NR subunit, and places its N-terminal extended helix into the axial groove of Nup205 from the neighboring subunit.

Single-particle cryo-EM structure of the NR subunit

Together with other structural information from the Shi lab, they have generated a composite atomic model of the central ring scaffold that includes the NR, IR, and CR, which is the most detailed and accurate structural model of the NPC scaffold to date. This model facilitates functional understanding of the vertebrate NPC.