Nevan J. Krogan

An extracellular substrate for the temporary storage of memories

The paper identifies aggrecan as an extracellular matrix protein that stabilizes fear memories by altering neuronal excitability in the hippocampal dentate gyrus.

Large scale prospective evaluation of co-folding across hundreds of Mac1-ligand complexes and three virtual screens

On 489 evaluable new Mac1 complexes, AlphaFold3, Chai-1 and Boltz-2 placed over half of ligands within 2 Å, but on docking hit-lists AF3 and Boltz-2 added little over docking.

Inhibiting the interaction between the mitochondrial receptor Tom70 and SARS CoV 2 Orf9b with small molecules

This paper identifies two strategies to modulate the Orf9b-Tom70 interaction by screening for small molecules that either stabilize Orf9b dimer or block its binding to Tom70, with potential to restore interferon signaling against SARS-CoV-2.

Secreted ORF8 reprograms macrophages to enhance SARS-CoV-2 infection of lung epithelial cells

This study shows that SARS-CoV-2's ORF8 protein reprograms macrophages to enhance viral infection of lung epithelial cells, contributing to lung pathology in COVID-19.

Multi-omics Reveals Divergent Endothelial Molecular Responses to New and Old World Hantaviruses

This study integrates multi-omics data to compare endothelial cell responses to New and Old World hantaviruses, identifying species-specific immune and cellular mechanisms.

An operon encoding two secreted nucleases mediates virulence in Methicillin-resistant Staphylococcus aureus

The paper identifies an operon in MRSA encoding two secreted nucleases that contribute to virulence, showing attenuation in a mouse model when mutated.

A de novo designed enzyme for photo-proximity labeling of E3 ligase neighborhoods in live cells

This paper introduces EYClamp, a de novo designed enzyme for photo-proximity labeling of E3 ligase neighborhoods in live cells, identifying over 1,500 candidate neighbors for four E3 ligases.

APOE4 disrupts the central dogma by arresting neuronal proteome dynamics

This study shows APOE4 disrupts neuronal proteome dynamics by impairing proteostasis, leading to protein accumulation and cellular stress before Alzheimer's disease onset.

Paracrine Signals from HIV-1 Infected Immune Cells Reprogram Cervical Cancer Pathways

This study shows HIV-1 infected immune cells alter cervical cancer pathways through paracrine signals, with upregulated PI3K-AKT and interferon-stimulated genes.

Coronavirus protein interaction mapping in bat and human cells identifies molecular and genetic switches for immune evasion and replication

Entry, replication and innate immunity evasion of BANAL-236, a SARS-CoV-2-related bat virus, in Rhinolophus and human cells

This study investigates BANAL-236, a SARS-CoV-2-related bat virus, showing it can use human entry factors and evade human innate immunity, suggesting potential for zoonotic spillover.

The COX2-PGE2-PKA Axis Suppresses Antiviral Immunity by Inhibiting mtDNA-Dependent STING Activation.

This study identifies the COX2-PGE2-PKA axis as a negative regulator of mtDNA-STING signaling, which suppresses antiviral immunity by inhibiting STING activation through mitophagy.

LANA-dependent Interaction of Host Factors DAXX and BRD4 Impact KSHV Lytic Replication

This paper identifies DAXX and BRD4 as LANA-interacting host factors that support KSHV latency, while LIG3 is required for lytic reactivation, revealing their roles in viral replication.

Discovery of AVI-6451, a Potent and Selective Inhibitor of the SARS-CoV-2 ADP-Ribosylhydrolase Mac1 with Oral Efficacy in vivo

This paper identifies AVI-6451, an orally bioavailable inhibitor of SARS-CoV-2 Mac1 with once-daily efficacy in a mouse model.

Functional diversification of the cephalopod proteome by RNA-editing

This study investigates how RNA editing in cephalopods alters protein function through proteomics and biochemical assays, revealing its impact on protein stability, localization, and interactions.

The Mac1 ADP-ribosylhydrolase is a Therapeutic Target for SARS-CoV-2

This study identifies Mac1 as a therapeutic target for SARS-CoV-2 and demonstrates that AVI-4206, a small molecule inhibitor, reduces viral replication and improves survival in an animal model.

Tax1bp1 enhances bacterial virulence and promotes inflammatory responses during Mycobacterium tuberculosis infection of alveolar macrophages

This study shows Tax1bp1 promotes Mtb growth in alveolar macrophages and enhances inflammatory responses, while restricting Mtb in bone marrow-derived macrophages.

Selective RNA sequestration in biomolecular condensates directs cell fate transitions

The paper profiles RNA content in P-bodies across vertebrate species, showing that RNA sequestration in condensates is linked to cell fate transitions through miRNA-dependent mechanisms.

Lysosomal proteomics reveals mechanisms of neuronal apoE4-associated lysosomal dysfunction

This study identifies lysosomal proteome changes caused by apoE4, linking them to lysosomal dysfunction and Alzheimer's disease pathology.

Ebola virus VP35 NNLNS motif modulates viral RNA synthesis and MIB2-mediated signaling

This study identifies and characterizes the NNLNS motif in Ebola virus VP35 that mediates MIB2 binding, inhibiting IFN production and affecting viral RNA synthesis.

Coupled equilibria of dimerization and lipid binding modulate SARS Cov 2 Orf9b interactions and interferon response

This study develops a biophysical model to show how lipid binding and mutations affect Orf9b's conformational equilibrium and its interaction with Tom70, influencing interferon suppression.

Programmable translational inhibition by a molecular glue-oligonucleotide conjugate

This paper develops RocASO, a molecular glue-oligonucleotide conjugate that selectively inhibits mRNA translation by targeting specific sequences, showing potent antiviral activity against SARS-CoV-2.

AlphaFold models of host-pathogen interactions elucidate the prevalence and structural modes of molecular mimicry

The paper uses AlphaFold to predict structures of host-pathogen PPIs, revealing molecular mimicry modes and convergent evolution of interaction interfaces.

Structure-based discovery of highly bioavailable, covalent, broad-spectrum coronavirus-MPro inhibitors with potent in vivo efficacy

This paper describes the discovery of new coronavirus MPro inhibitors with improved pharmacokinetics, broad-spectrum antiviral activity, and superior in vivo efficacy compared to existing drugs.

Enhanced RNA replication and pathogenesis in recent SARS-CoV-2 variants harboring the L260F mutation in NSP6

This study identifies the L260F mutation in NSP6 as enhancing RNA replication and pathogenesis in recent SARS-CoV-2 variants, independent of Spike function.

A proximity proteomics pipeline with improved reproducibility and throughput

This paper introduces a scalable proximity proteomics pipeline that improves reproducibility and throughput in biotinylation-based spatial proteomics.

Fate of telomere entanglements is dictated by the timing of anaphase midregion nuclear envelope breakdown

The paper shows that Rif1 delays nuclear envelope breakdown during anaphase, preventing resolution of telomere entanglements caused by Taz1 loss, leading to lethality.

The Chlamydia trachomatis Inc Tri1 interacts with TRAF7 to displace native TRAF7 interacting partners

This paper identifies the interaction between Chlamydia trachomatis effector Tri1 and host TRAF7, showing Tri1 displaces TRAF7's native binding partners to alter its signaling during infection.

Predicted mechanistic impacts of human protein missense variants

The paper predicts the mechanistic impacts of human protein missense variants on stability, protein-protein interactions, and small-molecule binding using AlphaFold2 structures.

Cell Maps for Artificial Intelligence: AI-Ready Maps of Human Cell Architecture from Disease-Relevant Cell Lines

The paper introduces the CM4AI project, which aims to create AI-ready datasets of human cell architecture using multimodal data from cell lines.