Functional Insights from Studies on the Structure of the Nuclear Pore and Coat Protein Complexes

Schwartz, Thomas

doi:10.1101/cshperspect.a013375

Cited by 7 publications

(5 citation statements)

References 79 publications

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“…The nuclear pore complex (NPC) is the largest non-polymeric protein complex in eukaryotic cells, embedded in a double membrane called the nuclear envelope (NE), and mediates all macromolecular transport across the NE. The NPC has an octameric structure and is composed of multiple copies of over 30 different proteins termed nucleoporins (Nups) ( Grossman et al, 2012 ; Schwartz, 2013 ; Strambio-De-Castillia et al, 2010 ). In metazoan cells NPCs are assembled in two cell-cycle stages, during nuclear assembly post anaphase and during nuclear growth in interphase.…”

Section: Introductionmentioning

confidence: 99%

Nuclear pore assembly proceeds by an inside-out extrusion of the nuclear envelope

Otsuka

Bui

Schorb

et al. 2016

eLife

166

247

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The nuclear pore complex (NPC) mediates nucleocytoplasmic transport through the nuclear envelope. How the NPC assembles into this double membrane boundary has remained enigmatic. Here, we captured temporally staged assembly intermediates by correlating live cell imaging with high-resolution electron tomography and super-resolution microscopy. Intermediates were dome-shaped evaginations of the inner nuclear membrane (INM), that grew in diameter and depth until they fused with the flat outer nuclear membrane. Live and super-resolved fluorescence microscopy revealed the molecular maturation of the intermediates, which initially contained the nuclear and cytoplasmic ring component Nup107, and only later the cytoplasmic filament component Nup358. EM particle averaging showed that the evagination base was surrounded by an 8-fold rotationally symmetric ring structure from the beginning and that a growing mushroom-shaped density was continuously associated with the deforming membrane. Quantitative structural analysis revealed that interphase NPC assembly proceeds by an asymmetric inside-out extrusion of the INM.DOI: http://dx.doi.org/10.7554/eLife.19071.001

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Section: Introductionmentioning

confidence: 99%

Nuclear pore assembly proceeds by an inside-out extrusion of the nuclear envelope

Otsuka

Bui

Schorb

et al. 2016

eLife

166

247

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“…The protocoatomer hypothesis suggests that a common membrane bending (or stabilizing) machinery arose early in evolution and later became specialized as a critical scaffold for the docking of nuclear pore complexes (NPCs) into the NE [2]. Indeed, the scaffold of the NPC is made up of about a dozen constituent proteins (called nucleoporins or nups) that bear a striking structural similarity to the clathrin and COP coat complexes [3]. The initial NPC membrane coat, which resides at the “pore membrane” where the inner and outer nuclear membranes converge, likely provided the structural basis for ensuring that all macromolecules were routed through pores in the NE (Fig.…”

Section: Establishing Stable Nuclear and Cytoplasmic Compartmentsmentioning

confidence: 99%

The nucleus: keeping it together by keeping it apart

Lusk

King

2017

Current Opinion in Cell Biology

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It has been postulated that the segregation of nucleus and cytoplasm supported the development of increased organismal complexity. For example, separating transcription and translation allows for mRNA splicing, while the sequestration of genomic DNA supports the innate immune system’s ability to equate cytoplasmic DNA with pathogens. Consistent with the importance of nucleocytoplasmic compartmentalization in a broad array of cellular processes, defects in maintaining discrete nuclear and cytoplasmic compartments, either due to loss of nuclear pore complex integrity, disrupted nuclear transport or ruptures of the nuclear envelope, lead to cellular dysfunction, cell death and disease. Here, we discuss recent insights into how loss of compartmentalization can arise as well as the consequences for cellular and organismal homeostasis.

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“…Yet, no sequence signature for ACE1 has ever been detected, either for Y-Nups/Nic96 or Sec31/Sec16, while the structure determination and comparison of these coatomers revealed this surprising structural similarity 10 . ACE1 might be considered as a structural manifestation of the likely common origin of NPC and COPII coats 12 , but has never been observed outside these complexes 14 . A combination of phylogenomic profiling and structural predictions has further extended this relationship to the intraflagellar transport complex (IFT) of the cilium 15 , across eukaryotic phyla and their representative genome sequences 16 .…”

Section: Main Textmentioning

confidence: 99%

Sequence evidence for common ancestry of eukaryotic endomembrane coatomers

Promponas

Katsani

Blencowe

et al. 2015

Preprint

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Eukaryotic cells are defined by compartments through which the trafficking of macromolecules is mediated by large complexes, such as the nuclear pore, transport vesicles and intraflagellar transport. The assembly and maintenance of these complexes is facilitated by endomembrane coatomers, long suspected to be divergently related on the basis of structural and more recently phylogenomic analysis. By performing supervised walks in sequence space across coatomer superfamilies, we uncover subtle sequence patterns that have remained elusive to date, ultimately unifying eukaryotic coatomers by divergent evolution. The conserved residues shared by 3,502 endomembrane coatomer components are mapped onto the solenoid superhelix of nucleoporin and COPII protein structures, thus determining the invariant elements of coatomer architecture. This ancient structural motif can be considered as a universal signature connecting eukaryotic coatomers involved in multiple cellular processes across cell physiology and human disease.Nuclear pore complexes (NPCs) are modular assemblies embedded at the points of fusion between the inner and outer membrane of the eukaryotic nucleus that mediate nucleocytoplasmic transport 1 . The overall architecture and composition of the NPCs is largely taxonomically conserved, indicating early origins in the eukaryotic tree 2 . In particular, nucleoporins including those at the outer ring coat forming the Y-complex (outer ring coat Nups or Y-Nups) share certain key structural and architectural similarities, possibly due to deep divergence [3][4][5] . These features extend beyond the nuclear pore, namely the COPII coat associated with anterograde transport from the rough endoplasmic reticulum to the Golgi apparatus and the COPI coat associated with the reverse, retrograde transport 6 , suggesting a common origin of endomembrane coatomers, one class of which is represented by the NPC coat 7 . The divergence of nucleoporin families has been proposed on the basis of global structural but no specific sequence evidence, especially for the Y-Nups 8 . This presumption is based on detailed structural analysis, presence of beta-propeller repeats at the N-terminus, an alpha-solenoid superhelix at the C-terminus and other architectural elements with regard to the multi-domain composition of Y-Nups 5,9 . In particular, the solenoid superhelix of the resolved structures for Nup75, Nup96, Nup107 (Y-Nups) and Nic96 -reminiscent of the tetratrico-peptide repeat (TPR) domain 10 -is also present in Sec31 and Sec16, building blocks of the COPII vesicle coat 11,12 . Much attention has been paid to this structural element as a common architectural motif across diverse coatomer molecules, and has thus been named Ancestral Coatomer Element 1 (ACE1) 11,13 , favouring the hypothesis of deep divergence over convergent evolution14 . Yet, no sequence signature for ACE1 has ever been detected, either for Y-Nups/Nic96 or Sec31/Sec16, while the structure determination and comparison of these coatomers revealed this surprising structu...

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Functional Insights from Studies on the Structure of the Nuclear Pore and Coat Protein Complexes

Cited by 7 publications

References 79 publications

Nuclear pore assembly proceeds by an inside-out extrusion of the nuclear envelope

Nuclear pore assembly proceeds by an inside-out extrusion of the nuclear envelope

The nucleus: keeping it together by keeping it apart

Sequence evidence for common ancestry of eukaryotic endomembrane coatomers

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