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Geometric shape matching for recovering protein conformations from single-particle Cryo-EM data

Announce Type: replace-cross Abstract: We address recovery of the three-dimensional backbone structure of single polypeptide proteins from single-particle cryo-electron microscopy (Cryo-SPA) data. Cryo-SPA produces noisy tomographic projections of electrostatic potentials of macromolecules. From these projections, we use methods from shape analysis to recover the three-dimensional backbone structure.

arXiv CS 9d ago

Two Datasets Are Better Than One: Method of Double Moments for 3-D Reconstruction in Cryo-EM

Announce Type: replace Abstract: Cryo-electron microscopy (cryo-EM) is a powerful imaging technique for reconstructing three-dimensional molecular structures from noisy tomographic projection images of randomly oriented particles. We introduce a new data fusion framework, termed the method of double moments (MoDM), which reconstructs molecular structures from two instances of the second-order moment of projection images obtained under distinct orientation distributions: one uniform, the...

arXiv CS 8d ago

Direct Detection and Atomic Modeling of Ligands in Cryo-EM Maps Using Deep Learning

Cryogenic electron microscopy (cryo-EM) has become an increasingly important for structure-based drug discovery by enabling characterization of interactions between macromolecules and small-molecule ligands. However, computational interpretation of ligand density remains challenging, particularly when ligand locations are unknown or local map resolution is limited. Existing methods generally require well-resolved macromolecular structures and predefined binding sites, limiting their...

bioRxiv 6d ago

Cryo-Bench: Benchmarking Foundation Models for Cryosphere Applications

arXiv:2603.01576v3 Announce Type: replace Abstract: Geo-Foundation Models (GFMs) have been evaluated across diverse Earth observation task including multiple domains and have demonstrated strong potential of producing reliable maps even with sparse labels. However, benchmarking GFMs for Cryosphere applications has remained limited, primarily due to the lack of suitable evaluation datasets. To address this gap, we introduce \textbf{Cryo-Bench}, a benchmark compiled to evaluate GFM performance...

arXiv CS 7d ago

Cryo-EM provides insight into how the Staphylococcus aureus IsdH receptor removes hemin from the hemoglobin:haptoglobin complex

Staphylococcus aureus extracts hemin from human hemoglobin (Hb) to overcome host-imposed iron limitation. How it recovers Hb-bound hemin from the hemoglobin:haptoglobin (Hb:Hp) complex, the major circulating form of Hb outside red blood cells, remains unclear. Here we use cryo-electron microscopy, biophysical measurements, and solution kinetics to define how the S. aureus IsdH surface receptor extracts hemin from Hb:Hp.

bioRxiv 2d ago

Unraveling the Mechanism of HIV-1 Hypersusceptibility to Tenofovir Imparted by Islatravir Resistance Mutations

In response to the newly approved antiretroviral therapy (ART) islatravir (ISL), the M184V and A114S resistance mutations have emerged in the human immunodeficiency virus type 1 reverse transcriptase (HIV-1 RT). These mutations markedly hypersensitize RT to the globally administered ART tenofovir disoproxil fumarate (TDF). We have solved six structures - four by X-ray crystallography and two by cryo-EM - that capture the single- and double-mutant RTs during inhibitor incorporation and...

bioRxiv 8d ago

DNA remodeling couples target recognition to directional transposition in a Tn7-like CAST

CRISPR-associated transposons (CASTs) couple target recognition to the insertion of large DNA cargoes, but how distinct targeting pathways are converted into productive and directional integration remains poorly understood1. Here we define the assembly pathway of a type I-B1 CAST from Anabaena variabilis, a system closely related to prototypical Tn7 that retains TnsD-mediated glmS recognition while incorporating CRISPR-based RNA-guided targeting2. Cryo-electron microscopy structures across...

bioRxiv 7d ago

A functional amyloid scaffold shapes insect egg coats

Functional amyloids serve as structural scaffolds across biology, yet the molecular architecture and assembly principles of many remain unresolved. The lepidopteran egg coat, or chorion, presents a striking example: hundreds of paralogous proteins sharing a conserved central domain assemble into a mechanically resilient amyloid matrix essential for embryo protection. Here, combining evolutionary analysis of more than 500 sequences with cryo-electron microscopy and biophysical assays, we...

bioRxiv 8d ago

Structural Dynamics of RNA Polymerase II During Nucleotide Addition Cycle

RNA polymerase II (RNAPII) drives gene expression through iterative nucleotide addition cycles (NACs) comprising translocation, substrate binding, and catalysis. The lack of pre-catalysis and post-catalysis intermediates has precluded a complete mechanistic understanding of the NAC. Here we present 43 cryo-EM structures capturing distinct stages of the S. cerevisiae RNAPII elongation complex (EC) NAC, including previously intractable transition intermediates.

bioRxiv 5d ago

A phage-encoded small RNA that mimics chimeric guide to inhibit CRISPR-Cas9

CRISPR Cas9 relies on a dual crRNA-tracrRNA guide, yet whether RNA based anti CRISPRs exist for this system has remained unknown. Here we identify a phage encoded small non coding RNA, rAcrIIA1, that adopts an unexpected chimeric crRNA-tracrRNA architecture, faithfully recapitulating the entire single guide RNA (sgRNA) of Cas9. Cryo EM structures of the Cas9-rAcrIIA1 binary complex and the Cas9-rAcrIIA1-DNA ternary complex reveal that rAcrIIA1 engages Cas9 nearly identically to the native...

bioRxiv 7d ago