Biology subjects

Glushkova, D.

Publications and source records attributed to Glushkova, D..

3 recordsLinked to original sources

bioRxiv2026

How the TREX-2 complex associates with the nuclear pore

Nuclear pore complexes (NPCs) control nucleocytoplasmic transport in eukaryotes, yet their architecture remains incompletely understood. Here we report a substantially extended structure of the human NPC, obtained by combining cryo-electron tomography, crosslinking mass spectrometry, and AI-assisted integrative modeling. We resolve the molecular arrangement of TPR, NUP153, NUP50 and ZC3HC1, and reveal that five additional proteins -- TMEM209, SMPD4, GANP, Centrin-2 and ENY2 -- are incorporated into the NPC. Unexpectedly, GANP, Centrin-2 and ENY2, core members of the TREX-2 mRNA export complex, are built into the nuclear ring. This finding establishes TREX-2 not as a transiently associated factor, but as an integral NPC module, positioning it opposite of the cytoplasmic NUP214 mRNA export platform. Together, our results redefine the molecular composition of the inner ring, nuclear ring and nuclear basket. They suggest a direct structural basis that couples TREX-2-mediated mRNP remodeling to NPC-facilitated transport.

cell biology↗

bioRxiv2025

The vault associates with membranes in situ

The eukaryotic vault particle is a giant ribonucleoprotein complex that assembles into an iconic barrel-like cage. Its cellular function has remained elusive despite extensive characterization. Using cryo-electron tomography of Dictyostelium discoideum cells, we define the distribution, structural states and interaction landscape of vault particles in situ. Surprisingly, we detect a subpopulation of vault particles associated with the endoplasmic reticulum (ER) and nuclear envelope membranes. This association occurs at a defined barrel height of the vault particle and at patches of reduced membrane bilayer thickness and altered curvature. We further find that a substantial fraction of vaults encloses 80S ribosomes in highly ordered orientations. These structural findings are further corroborated by proximity labeling experiments which identify ER-resident proteins and numerous ribosomal components as vault particle interactors. The membrane-bound and ribosome-encapsulating vault populations that we uncover will direct future studies towards revealing vault function.

cell biology↗

bioRxiv2025

In situ evidence for systematic membrane thickness variation across cellular organelles

In eukaryotes, membrane-bound organelles create distinct molecular environments. The compartmentalizing lipid bilayer is a dynamic composite material, whose thickness and curvature modulate the structure and function of membrane proteins. In vitro, bilayer thickness correlates with lipid composition. Cellular membranes in situ, however, are continuously remodeled and the spatial variation of their biophysical properties remains understudied. Here, we present a computational approach to measure local membrane thickness in cryo-electron tomograms. Analysis of Chlamydomonas reihardtii and human cells reveals systematic thickness variations within and across organelles. These findings orthogonally support models of hydrophobic matching for differential sorting of proteins based on their transmembrane domain lengths, e.g., across the Golgi apparatus. Our workflow is computationally efficient, public, easy to integrate within existing tomogram analysis pipelines, and enables membrane thickness measurements across experimental conditions. Using this approach, relationships between membrane composition, thickness, and function are explored in situ, with broader applications across membrane biology.

biophysics↗