Cryo-EM structure of the nuclear ring from Xenopus laevis nuclear pore complex

Huang, Guangli; Zhan, Xiechao; Zeng, Chao; Zhu, Xinhui; Liang, Ke; Zhao, Yanyu; Wang, Pan; Wang, Qifan; Zhou, Qiang; Tao, Qinghua; Liu, Minhao; Lei, Jianlin; Yan, Chuangye; Shi, Yigong

doi:10.1038/s41422-021-00610-w

Cited by 26 publications

(20 citation statements)

References 51 publications

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“…As in our model of the IFT-A complex, stable interactions between TPR domains underlie diverse macromolecular assemblies. COPI PDB: 5A1W (116), COPII PDB: 6ZL0 (117), apoptosome PDB: 5JUY (118), anaphase promoting complex PDB: 5G05 (119), elongator complex PDB: 5CQR (73), nuclear pore complex PDB: 7WB4 (120).…”

Section: Discussionmentioning

confidence: 99%

Integrative modeling reveals the molecular architecture of the Intraflagellar Transport A (IFT-A) complex

McCafferty

Papoulas

Jordan

et al. 2022

Preprint

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Cilia are deeply conserved eukaryotic organelles that are essential to proper embryonic development in vertebrates through their roles in motility and signaling. Both ciliary assembly (ciliogenesis) and the movement of cargo along the ciliary axoneme depend on intraflagellar transport (IFT), which is executed through a super-assembly of motor proteins and cargo adaptors. The IFT core complexes, IFT-A and IFT-B, are hotspots for disease variants that lead to ciliopathies, genetic diseases resulting from ciliary dysfunction. To date, the structures of many IFT-associated protein complexes have yet to be well-characterized. Here, we combined chemical cross-linking mass spectrometry of intact complexes, AlphaFold2-predicted protein structures, and cryo-electron tomography to perform integrative modeling to define the overall architecture of the 6-subunit IFT-A complex. Crucially, our model is consistent with a wide array of existing biochemical data. The packing of IFT-A highlights preferred interaction modes made by proteins exhibiting similar domain architectures. We use this model to provide insights into the pleiotropic nature of genetic variants in IFT-A that are associated with human ciliopathies. Our work demonstrates the power of integrative modeling both for multi-protein structure determination and for understanding the etiology of human genetic disease.

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Section: Discussionmentioning

confidence: 99%

Integrative modeling reveals the molecular architecture of the Intraflagellar Transport A (IFT-A) complex

McCafferty

Papoulas

Jordan

et al. 2022

Preprint

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“…The association between Nup93-α5 and Nup205-CTD is almost identical to that observed in the IR and NR subunits (fig. S33) (18)(19)(20)(21).…”

Section: Nup93 Bridges the Y Complexes And Nup205mentioning

confidence: 99%

Near-atomic Structure of the Cytoplasmic Ring of the Xenopus laevis Nuclear Pore Complex

Zhu

Huang

Zeng

et al. 2022

Preprint

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The nuclear pore complex (NPC) mediates nucleocytoplasmic shuttling. Here we present single-particle cryo-EM structure of the cytoplasmic ring (CR) from the Xenopus laevis NPC at 4.1-4.7 Å resolutions. The structure of an N-terminal domain of Nup358 was resolved at 3.0 Å, facilitating identification of five Nup358 molecules in each CR subunit. Aside from unveiling the assembly details of the two Y-shaped multicomponent complexes (Y complexes) in each CR subunit, the improved resolutions reveal the C-terminal fragment of Nup160 to be an organizing center at the vertex of each Y complex. Our structures show that the scaffold of a CR subunit comprises five Nup358, two Nup205 and two Nup93 molecules in addition to the previously characterized Y complexes.

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“…These mechanisms enable the movement of proteins, RNAs, and a diverse array of molecules, including lipids, across the nuclear envelope. They rely on nuclear pore complexes for active transport and use passive diffusion or vesicular transport for smaller, non-polar, and uncharged substances (Akey et al, 2022; Fernandez-Martinez et al, 2016; Fontana et al, 2022; Huang et al, 2022; Manik et al, 2017; Zhu et al, 2022).…”

Section: Introductionmentioning

confidence: 99%

Nuclear Lipid Droplets Exit to the Cytoplasm: A Novel Mechanism of non-nuclear pore-dependent material exchange

Jin,

Huang,

Zhao

et al. 2023

Preprint

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In cellular biology, the extrusion of large molecular complexes from the nucleus has consistently represented a considerable challenge. In this investigation, we reveal a hitherto unexplored mechanism facilitating the efflux of nuclear lipid droplets (nLDs) from the nucleus directly into the cytoplasm, a process integral to comprehending cellular processes and nuclear dynamics. Through high-throughput sequencing, immunoprecipitation, and immunofluorescence experimentation, we demonstrated that the type I nucleoplasmic reticulum engages with nLDs, enabling the dynamic protein Rab8a’s transfer to the nLDs and fostering their translocation to the nuclear membrane. Phosphorylation of LMNA/C at the S392 site, adjacent to the nLD-nuclear membrane contact site, induces local depolymerization of lamins, creating an aperture that enables gradual nuclear exit of nLDs. Following this, nLDs, carrying DNA fragments, are released into the cytoplasm through budding and subsequently undergo autophagy-mediated degradation. Furthermore, we demonstrate that RhoA-PKC signaling enhances nLD movement and LMNA/C phosphorylation, while its inhibition impedes nuclear nLD efflux. Our groundbreaking investigation illuminates non-nuclear pore-dependent mechanisms of material exchange and offers fresh perspectives on nuclear metabolic pathways.In BriefIn this study, Jin et al. elucidate a novel mechanism for the expulsion of nuclear lipid droplets (nLDs) from the nucleus. They demonstrate that the activation of RhoA within the nucleus recruits Rab8a to the surface of nLDs. Concurrently, PKC phosphorylation triggers the phosphorylation of LMNA/C at the S392 site, leading to a localized depolymerization of lamins. This creates an aperture that allows for the gradual exit of nLDs from the nucleus. The efflux process of nLDs involves three sequential steps: rupture of the nuclear fibril layer, fusion of nLDs with the inner nuclear membrane (INM), and subsequent fusion with the outer nuclear membrane (ONM). This enables nLDs to enter the cytoplasm, shedding light on a previously unknown process of large molecular entity expulsion from the nucleus.

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Cryo-EM structure of the nuclear ring from Xenopus laevis nuclear pore complex

Cited by 26 publications

References 51 publications

Integrative modeling reveals the molecular architecture of the Intraflagellar Transport A (IFT-A) complex

Integrative modeling reveals the molecular architecture of the Intraflagellar Transport A (IFT-A) complex

Near-atomic Structure of the Cytoplasmic Ring of the Xenopus laevis Nuclear Pore Complex

Nuclear Lipid Droplets Exit to the Cytoplasm: A Novel Mechanism of non-nuclear pore-dependent material exchange

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