Alberto Bartesaghi

Journal Article Proc Natl Acad Sci U S A · August 6, 2024 Invasive fungal diseases are a major threat to human health, resulting in more than 1.5 million annual deaths worldwide. The arsenal of antifungal therapeutics remains limited and is in dire need of drugs that target additional biosynthetic pathways that a ... Full text Link to item Cite

Advances in cryo-ET data processing: meeting the demands of visual proteomics.

Journal Article Current opinion in structural biology · August 2024 Cryogenic electron tomography (cryo-ET), a method that enables the viewing of biomolecules in near-native environments at high resolution, is rising in accessibility and applicability. Over the past several years, once slow sample preparation and data coll ... Full text Cite

Structures of trehalose-6-phosphate synthase, Tps1, from the fungal pathogen Cryptococcus neoformans : a target for novel antifungals.

Preprint · June 5, 2024 Full text Link to item Cite

Joint micrograph denoising and protein localization in cryo-electron microscopy.

Journal Article Biological imaging · January 2024 Cryo-electron microscopy (cryo-EM) is an imaging technique that allows the visualization of proteins and macromolecular complexes at near-atomic resolution. The low electron doses used to prevent radiation damage to the biological samples result in images ... Full text Cite

Mouse α-synuclein fibrils are structurally and functionally distinct from human fibrils associated with Lewy body diseases

Preprint · 2024 Full text Cite

nextPYP: a comprehensive and scalable platform for characterizing protein variability in situ using single-particle cryo-electron tomography.

Journal Article Nature methods · December 2023 Single-particle cryo-electron tomography is an emerging technique capable of determining the structure of proteins imaged within the native context of cells at molecular resolution. While high-throughput techniques for sample preparation and tilt-series ac ... Full text Cite

Molecular architecture and conservation of an immature human endogenous retrovirus.

Journal Article Nature communications · August 2023 The human endogenous retrovirus K (HERV-K) is the most recently acquired endogenous retrovirus in the human genome and is activated and expressed in many cancers and amyotrophic lateral sclerosis. We present the immature HERV-K capsid structure at 3.2 Å re ... Full text Cite

Expanding the Reach of Cryo-EM through Open Design Robotics and Remote Screening.

Journal Article Microsc Microanal · July 22, 2023 Full text Link to item Cite

Molecular architecture and conservation of an immature human endogenous retrovirus.

Journal Article bioRxiv · June 7, 2023 A significant part of the human genome consists of endogenous retroviruses sequences. Human endogenous retrovirus K (HERV-K) is the most recently acquired endogenous retrovirus, is activated and expressed in many cancers and amyotrophic lateral sclerosis a ... Full text Link to item Cite

Structural basis for breadth development in the HIV-1 V3-glycan targeting DH270 antibody clonal lineage.

Journal Article Nat Commun · May 15, 2023 Antibody affinity maturation enables adaptive immune responses to a wide range of pathogens. In some individuals broadly neutralizing antibodies develop to recognize rapidly mutating pathogens with extensive sequence diversity. Vaccine design for pathogens ... Full text Link to item Cite

Structure and dynamics of the Arabidopsis O-fucosyltransferase SPINDLY.

Journal Article Nat Commun · March 20, 2023 SPINDLY (SPY) in Arabidopsis thaliana is a novel nucleocytoplasmic protein O-fucosyltransferase (POFUT), which regulates diverse developmental processes. Sequence analysis indicates that SPY is distinct from ER-localized POFUTs and contains N-terminal tetr ... Full text Open Access Link to item Cite

Multiple-image super-resolution of cryo-electron micrographs based on deep internal learning.

Journal Article Biological imaging · January 2023 Single-particle cryo-electron microscopy (cryo-EM) is a powerful imaging modality capable of visualizing proteins and macromolecular complexes at near-atomic resolution. The low electron-doses used to prevent radiation damage to the biological samples, how ... Full text Cite

Automated systematic evaluation of cryo-EM specimens with SmartScope.

Journal Article Elife · August 23, 2022 Finding the conditions to stabilize a macromolecular target for imaging remains the most critical barrier to determining its structure by cryo-electron microscopy (cryo-EM). While automation has significantly increased the speed of data collection, specime ... Full text Link to item Cite

High-resolution structure determination using high-throughput electron cryo-tomography.

Journal Article Acta crystallographica. Section D, Structural biology · July 2022 Tomographic reconstruction of frozen-hydrated specimens followed by extraction and averaging of sub-tomograms has successfully been used to determine the structure of macromolecules in their native environment at resolutions that are high enough to reveal ... Full text Cite

Data-driven determination of number of discrete conformations in single-particle cryo-EM.

Journal Article Computer methods and programs in biomedicine · June 2022 Background and objectiveOne of the strengths of single-particle cryo-EM compared to other structural determination techniques is its ability to image heterogeneous samples containing multiple molecular species, different oligomeric states or disti ... Full text Cite

Redox-sensitive E2 Rad6 controls cellular response to oxidative stress via K63-linked ubiquitination of ribosomes.

Journal Article Cell Rep · May 24, 2022 Protein ubiquitination is an essential process that rapidly regulates protein synthesis, function, and fate in dynamic environments. Within its non-proteolytic functions, we showed that K63-linked polyubiquitinated conjugates heavily accumulate in yeast ce ... Full text Link to item Cite

Structural basis of NPR1 in activating plant immunity.

Journal Article Nature · May 2022 NPR1 is a master regulator of the defence transcriptome induced by the plant immune signal salicylic acid1-4. Despite the important role of NPR1 in plant immunity5-7, understanding of its regulatory mechanisms has been hindered by a lack of structural info ... Full text Link to item Cite

Weakly Supervised Learning for Joint Image Denoising and Protein Localization in Cryo-Electron Microscopy

Conference Proceedings - 2022 IEEE/CVF Winter Conference on Applications of Computer Vision, WACV 2022 · January 1, 2022 Deep learning-based object detection methods have shown promising results in various fields ranging from autonomous driving to video surveillance where input images have relatively high signal-to-noise ratios (SNR). On low SNR images such as biological ele ... Full text Cite

Structural and functional landscape of α-synuclein fibril conformations amplified from cerebrospinal fluid

Preprint · 2022 Full text Cite

Accurate Detection of Proteins in Cryo-Electron Tomograms from Sparse Labels

Conference Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics) · January 1, 2022 Cryo-electron tomography (CET) combined with sub-volume averaging (SVA), is currently the only imaging technique capable of de-termining the structure of proteins imaged inside cells at molecular reso-lution. To obtain high-resolution reconstructions, sub- ... Full text Cite

Structures of trehalose-6-phosphate synthase, Tps1, from the fungal pathogen Cryptococcus neoformans: A target for antifungals.

Advances in cryo-ET data processing: meeting the demands of visual proteomics.

Structures of trehalose-6-phosphate synthase, Tps1, from the fungal pathogen Cryptococcus neoformans : a target for novel antifungals.

Preprint · June 5, 2024 Full text Link to item Cite

Joint micrograph denoising and protein localization in cryo-electron microscopy.

Mouse α-synuclein fibrils are structurally and functionally distinct from human fibrils associated with Lewy body diseases

Preprint · 2024 Full text Cite

nextPYP: a comprehensive and scalable platform for characterizing protein variability in situ using single-particle cryo-electron tomography.

Molecular architecture and conservation of an immature human endogenous retrovirus.

Expanding the Reach of Cryo-EM through Open Design Robotics and Remote Screening.

Journal Article Microsc Microanal · July 22, 2023 Full text Link to item Cite

Molecular architecture and conservation of an immature human endogenous retrovirus.

Structural basis for breadth development in the HIV-1 V3-glycan targeting DH270 antibody clonal lineage.

Structure and dynamics of the Arabidopsis O-fucosyltransferase SPINDLY.

Multiple-image super-resolution of cryo-electron micrographs based on deep internal learning.

Automated systematic evaluation of cryo-EM specimens with SmartScope.

High-resolution structure determination using high-throughput electron cryo-tomography.

Data-driven determination of number of discrete conformations in single-particle cryo-EM.

Redox-sensitive E2 Rad6 controls cellular response to oxidative stress via K63-linked ubiquitination of ribosomes.

Structural basis of NPR1 in activating plant immunity.

Weakly Supervised Learning for Joint Image Denoising and Protein Localization in Cryo-Electron Microscopy

Structural and functional landscape of α-synuclein fibril conformations amplified from cerebrospinal fluid

Preprint · 2022 Full text Cite

Accurate Detection of Proteins in Cryo-Electron Tomograms from Sparse Labels

Preprint · 2022 Full text Cite

Automated systematic evaluation of cryo-EM specimens with SmartScope

Preprint · 2022 Full text Cite

Beam image-shift accelerated data acquisition for near-atomic resolution single-particle cryo-electron tomography

Conference Acta Crystallographica Section A Foundations and Advances · July 30, 2021 Full text Cite

Fab-dimerized glycan-reactive antibodies are a structural category of natural antibodies.

Journal Article Cell · May 27, 2021 Natural antibodies (Abs) can target host glycans on the surface of pathogens. We studied the evolution of glycan-reactive B cells of rhesus macaques and humans using glycosylated HIV-1 envelope (Env) as a model antigen. 2G12 is a broadly neutralizing Ab (b ... Full text Open Access Link to item Cite

Beam image-shift accelerated data acquisition for near-atomic resolution single-particle cryo-electron tomography.

Journal Article Nat Commun · March 30, 2021 Featured Publication Tomographic reconstruction of cryopreserved specimens imaged in an electron microscope followed by extraction and averaging of sub-volumes has been successfully used to derive atomic models of macromolecules in their biological environment. Eliminating bio ... Full text Link to item Cite

Structural Basis for Virulence Activation of Francisella tularensis.

Journal Article Mol Cell · January 7, 2021 The bacterium Francisella tularensis (Ft) is one of the most infectious agents known. Ft virulence is controlled by a unique combination of transcription regulators: the MglA-SspA heterodimer, PigR, and the stress signal, ppGpp. MglA-SspA assembles with th ... Full text Link to item Cite

Smartscope: AI-driven grid navigation for high-throughput cryo-EM

Conference Proceedings - Applied Imagery Pattern Recognition Workshop · January 1, 2021 Specimen optimization is currently one of the main limiting steps in the cryo-electron microscopy (EM) structure determination pipeline. The ideal specimen is a molecule-thin layer of macromolecules in solution frozen on top of a holey membrane stabilized ... Full text Cite

Joint Model for Image Denoising and Detection of Proteins Imaged by Cryo-EM

Conference Proceedings - Applied Imagery Pattern Recognition Workshop · January 1, 2021 Particle picking is a critical step in the single-particle cryo-electron microscopy (EM) structure determination pipeline. In order to successfully obtain the 3D reconstruction of a macro-molecular complex, hundreds of thousands of particles need to be acc ... Full text Cite

Cryo-ZSSR: multiple-image super-resolution based on deep internal learning

Journal Article · November 22, 2020 Single-particle cryo-electron microscopy (cryo-EM) is an emerging imaging modality capable of visualizing proteins and macro-molecular complexes at near-atomic resolution. The low electron-doses used to prevent sample radiation damage, result in images whe ... Link to item Cite

Structural impact of K63 ubiquitin on yeast translocating ribosomes under oxidative stress.

Journal Article Proc Natl Acad Sci U S A · September 8, 2020 Subpopulations of ribosomes are responsible for fine tuning the control of protein synthesis in dynamic environments. K63 ubiquitination of ribosomes has emerged as a new posttranslational modification that regulates protein synthesis during cellular respo ... Full text Link to item Cite

Single-particle cryo-electron microscopy: Mathematical theory, computational challenges, and opportunities.

Journal Article IEEE signal processing magazine · March 2020 In recent years, an abundance of new molecular structures have been elucidated using cryo-electron microscopy (cryo-EM), largely due to advances in hardware technology and data processing techniques. Owing to these new exciting developments, cryo-EM was se ... Full text Cite

Disruption of the HIV-1 Envelope allosteric network blocks CD4-induced rearrangements.

Journal Article Nat Commun · January 24, 2020 The trimeric HIV-1 Envelope protein (Env) mediates viral-host cell fusion via a network of conformational transitions, with allosteric elements in each protomer orchestrating host receptor-induced exposure of the co-receptor binding site and fusion element ... Full text Link to item Cite

Unsupervised particle sorting for high-resolution single-particle cryo-EM

Journal Article Inverse Problems · January 1, 2020 Single-particle cryo-electron microscopy (EM) has become a popular technique for determining the structure of challenging biomolecules that are inaccessible to other technologies. Recent advances in automation, both in data collection and data processing, ... Full text Cite

Single-Particle Cryo-Electron Microscopy: Mathematical Theory, Computational Challenges, and Opportunities.

Journal Article IEEE Signal Process. Mag. · 2020 Full text Cite

Streamlining Workflows for Structure Determination by Single Particle Cryo-EM

Conference Biophysical Journal · February 2019 Full text Cite

A Practical Guide to Multi-Image Alignment

Journal Article ICASSP, IEEE International Conference on Acoustics, Speech and Signal Processing - Proceedings · September 10, 2018 Multi-image alignment, bringing a group of images into common register, is an ubiquitous problem and the first step of many applications in a wide variety of domains. As a result, a great amount of effort is being invested in developing efficient multi-ima ... Full text Cite

Publisher Correction: Cryo-EM structure of human rhodopsin bound to an inhibitory G protein.

Journal Article Nature · September 2018 In the PDF version of this Article, owing to a typesetting error, an incorrect figure was used for Extended Data Fig. 5; the correct figure was used in the HTML version. This has been corrected online. ... Full text Cite

Single-particle cryo-EM structure of a voltage-activated potassium channel in lipid nanodiscs.

Journal Article eLife · August 2018 Voltage-activated potassium (Kv) channels open to conduct K+ ions in response to membrane depolarization, and subsequently enter non-conducting states through distinct mechanisms of inactivation. X-ray structures of detergent-solubilized Kv chan ... Full text Cite

Atomic Resolution Cryo-EM Structure of β-Galactosidase.

Journal Article Structure (London, England : 1993) · June 2018 Featured Publication The advent of direct electron detectors has enabled the routine use of single-particle cryo-electron microscopy (EM) approaches to determine structures of a variety of protein complexes at near-atomic resolution. Here, we report the development of methods ... Full text Cite

Cryo-EM structure of human rhodopsin bound to an inhibitory G protein.

Journal Article Nature · June 2018 Featured Publication G-protein-coupled receptors comprise the largest family of mammalian transmembrane receptors. They mediate numerous cellular pathways by coupling with downstream signalling transducers, including the hetrotrimeric G proteins Gs (stimulatory) and ... Full text Cite

Cryo-EM Structures Reveal Mechanism and Inhibition of DNA Targeting by a CRISPR-Cas Surveillance Complex.

Journal Article Cell · October 2017 Featured Publication Prokaryotic cells possess CRISPR-mediated adaptive immune systems that protect them from foreign genetic elements, such as invading viruses. A central element of this immune system is an RNA-guided surveillance complex capable of targeting non-self DNA or ... Full text Cite

Cryo-EM Tomographic Analysis of a Universal Influenza Virus Vaccine Candidate

Conference Biophysical Journal · February 2017 Full text Cite

Fundamental limits in multi-image alignment

Journal Article IEEE Transactions on Signal Processing · November 1, 2016 Featured Publication The performance of multiimage alignment, bringing different images into one coordinate system, is critical in many applications with varied signal-to-noise ratio (SNR) conditions. A great amount of effort is being invested into developing methods to solve ... Full text Cite

Cryo-EM Analysis of the Conformational Landscape of Human P-glycoprotein (ABCB1) During its Catalytic Cycle.

Journal Article Mol Pharmacol · July 2016 The multidrug transporter P-glycoprotein (P-gp, ABCB1) is an ATP-dependent pump that mediates the efflux of structurally diverse drugs and xenobiotics across cell membranes, affecting drug pharmacokinetics and contributing to the development of multidrug r ... Full text Link to item Cite

Using Cryo-EM to Map Small Ligands on Dynamic Metabolic Enzymes: Studies with Glutamate Dehydrogenase.

Journal Article Mol Pharmacol · June 2016 Cryo-electron microscopy (cryo-EM) methods are now being used to determine structures at near-atomic resolution and have great promise in molecular pharmacology, especially in the context of mapping the binding of small-molecule ligands to protein complexe ... Full text Link to item Cite

Breaking Cryo-EM Resolution Barriers to Facilitate Drug Discovery.

Journal Article Cell · June 2016 Featured Publication Recent advances in single-particle cryoelecton microscopy (cryo-EM) are enabling generation of numerous near-atomic resolution structures for well-ordered protein complexes with sizes ≥ ∼200 kDa. Whether cryo-EM methods are equally useful for high-resoluti ... Full text Cite

Cryo-electron Microscopy Structures of Chimeric Hemagglutinin Displayed on a Universal Influenza Vaccine Candidate.

Journal Article mBio · March 2016 UnlabelledInfluenza viruses expressing chimeric hemagglutinins (HAs) are important tools in the quest for a universal vaccine. Using cryo-electron tomography, we have determined the structures of a chimeric HA variant that comprises an H1 stalk an ... Full text Cite

Cryo-EM Structures of the Magnesium Channel CorA Reveal Symmetry Break upon Gating.

Journal Article Cell · February 11, 2016 CorA, the major Mg(2+) uptake system in prokaryotes, is gated by intracellular Mg(2+) (KD ∼ 1-2 mM). X-ray crystallographic studies of CorA show similar conformations under Mg(2+)-bound and Mg(2+)-free conditions, but EPR spectroscopic studies reveal large ... Full text Link to item Cite

Structures of the Mg2+ Channel Cora in the Open State by Cryo Electron Microscopy

Conference Biophysical Journal · February 2016 Full text Cite

Using cryo-EM to Untangle the Conformational Landscape of a Small Allosterically-Regulated Complex

Conference Biophysical Journal · February 2016 Full text Cite

Single-Particle Cryo-EM Studies of a 200-kDa Magnesium Ion Channel Reveal Large Structural Changes Upon Gating

Conference Biophysical Journal · February 2016 Full text Cite

2.3 Å resolution cryo-EM structure of human p97 and mechanism of allosteric inhibition.

Journal Article Science (New York, N.Y.) · February 2016 p97 is a hexameric AAA+ adenosine triphosphatase (ATPase) that is an attractive target for cancer drug development. We report cryo-electron microscopy (cryo-EM) structures for adenosine diphosphate (ADP)-bound, full-length, hexameric wild-type p97 in the p ... Full text Cite

2.2 Å resolution cryo-EM structure of β-galactosidase in complex with a cell-permeant inhibitor.

Journal Article Science (New York, N.Y.) · June 2015 Cryo-electron microscopy (cryo-EM) is rapidly emerging as a powerful tool for protein structure determination at high resolution. Here we report the structure of a complex between Escherichia coli β-galactosidase and the cell-permeant inhibitor phenylethyl ... Full text Cite

Localization of Small Ligands in a Metabolic Protein Complex using Cryo-Electron Microscopy

Conference Biophysical Journal · January 2015 Full text Cite

Structural Mechanism of Glutamate Receptor Activation and Desensitization

Conference Biophysical Journal · January 2015 Full text Cite

Residue Specific Radiation Damage of Protein Structures using High-Resolution Cryo-Electron Microscopy

Conference Biophysical Journal · January 2015 Full text Cite

Structural mechanism of glutamate receptor activation and desensitization.

Journal Article Nature · October 2014 Ionotropic glutamate receptors are ligand-gated ion channels that mediate excitatory synaptic transmission in the vertebrate brain. To gain a better understanding of how structural changes gate ion flux across the membrane, we trapped rat AMPA (α-amino-3-h ... Full text Cite

Spatial localization of the Ebola virus glycoprotein mucin-like domain determined by cryo-electron tomography.

Journal Article Journal of virology · September 2014 The Ebola virus glycoprotein mucin-like domain (MLD) is implicated in Ebola virus cell entry and immune evasion. Using cryo-electron tomography of Ebola virus-like particles, we determined a three-dimensional structure for the full-length glycoprotein in a ... Full text Cite

Accelerating discovery in 3D microanalysis: Leveraging open source software and deskside high performance computing

Conference Microscopy and Microanalysis · August 1, 2014 Full text Cite

Structure of β-galactosidase at 3.2-Å resolution obtained by cryo-electron microscopy.

Journal Article Proceedings of the National Academy of Sciences of the United States of America · August 2014 We report the solution structure of Escherichia coli β-galactosidase (∼465 kDa), solved at ∼3.2-Å resolution by using single-particle cryo-electron microscopy (cryo-EM). Densities for most side chains, including those of residues in the active site, and a ... Full text Cite

Structure Determination of Small Macromolecular Complexes by Cryo-Electron Microscopy

Conference Biophysical Journal · January 2014 Full text Cite

Prefusion structure of trimeric HIV-1 envelope glycoprotein determined by cryo-electron microscopy.

Journal Article Nat Struct Mol Biol · December 2013 The activation of trimeric HIV-1 envelope glycoprotein (Env) by its binding to the cell-surface receptor CD4 and co-receptors (CCR5 or CXCR4) represents the first of a series of events that lead to fusion between viral and target-cell membranes. Here, we p ... Full text Link to item Cite

HIV-1 envelope glycoprotein trimers display open quaternary conformation when bound to the gp41 membrane-proximal external-region-directed broadly neutralizing antibody Z13e1.

Journal Article Journal of virology · June 2013 We describe cryo-electron microscopic studies of the interaction between the ectodomain of the trimeric HIV-1 envelope glycoprotein (Env) and Z13e1, a broadly neutralizing antibody that targets the membrane-proximal external region (MPER) of the gp41 subun ... Full text Cite

Glutamate receptor desensitization is mediated by changes in quaternary structure of the ligand binding domain.

Journal Article Proc Natl Acad Sci U S A · April 9, 2013 Glutamate receptor ion channels are membrane proteins that mediate excitatory synaptic transmission in the central nervous system of vertebrates. Insight into molecular mechanisms underlying glutamate receptor gating is limited by lack of structural inform ... Full text Link to item Cite

A collaborative framework for 3D alignment and classification of heterogeneous subvolumes in cryo-electron tomography.

Journal Article J Struct Biol · February 2013 The limitation of using low electron doses in non-destructive cryo-electron tomography of biological specimens can be partially offset via averaging of aligned and structurally homogeneous subsets present in tomograms. This type of sub-volume averaging is ... Full text Link to item Cite