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Zamanos, A.

Publications and source records attributed to Zamanos, A..

2 recordsLinked to original sources

A 37-million-particle dataset from over 250 experiments to accelerate data-driven cryo-EM analysis

Cryogenic Electron Microscopy (cryo-EM) has revolutionized structural biology by enabling near-atomic-resolution structure determination of biological macromolecules. Central to cryo-EM analysis are particles, namely 2D projections of biomolecules extracted from micrographs, which serve as the primary input for 3D reconstruction. While data-driven methods have transformed other scientific domains, their impact on cryo-EM remains limited because existing particle datasets are too small, too narrow in protein diversity, and lack rich per-particle annotations. We introduce cryoPANDA (cryo-EM Particles ANnotated DAtaset), comprising over 37 million annotated particles from 252 experiments spanning a wide range of protein types, more than 10-fold larger than prior collections. Each particle is accompanied by detailed annotations covering acquisition, classification, and re-construction metadata, alongside the corresponding 3D electrostatic potential map, the published EMDB map, and, where available, the PDB model. We validate cryoPANDA in two ways: first, by reconstructing hundreds of distinct high-resolution cryo-EM maps; and second, by training a DINOv2 foundation model and evaluating its learned representations on micrograph segmentation, particle picking, and particle clustering.

bioinformatics↗

Cytosolic termini of the FurE transporter regulate endocytosis, pH-dependent gating and specificity

FurE, a member of the NCS1 family, is an Aspergillus nidulans transporter specific for uracil, allantoin and uric acid. Recently we showed that C- or N-terminally truncated FurE versions are blocked for endocytosis and, surprisingly, show modified substrate specifities. Bifluorescence complementation assays and genetic analyses supported that the C- and N-termini interact dynamically and through this interaction regulate selective substrate translocation. Here we functionally dissect and delimit distinct motifs crucial for endocytosis, transport activity, substrate specificity and folding, in both cytosolic termini of FurE. Subsequently, we obtain novel genetic and in silico evidence supporting that the molecular dynamics of specific N- and C-terminal regions affect allosterically the gating mechanism responsible for substrate selection, via pH-dependent interactions with other internal cytosolic loops and membrane lipids. Our work shows that elongated cytoplasmic termini, acquired through evolution mostly in eukaryotic transporters, provide novel specific functional roles.

molecular biology↗