Structural basis for breadth development in the HIV-1 V3-glycan targeting DH270 antibody clonal lineage 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 such as HIV-1 and influenza has therefore focused on recapitulating the natural…
Molecular architecture and conservation of an immature human endogenous retrovirus 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 resolution determined from native virus-like particles using cryo-electron tomography and subtomogram…
nextPYP: a comprehensive and scalable platform for characterizing protein variability in situ using single-particle cryo-ET Single-particle cryo-electron tomography (SP-CET) 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 acquisition are beginning to provide sufficient data to allow structural studies…
Joint micrograph denoising and protein localization in cryo-electron microscopy 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 where the power of noise is 100 times stronger than that of the signal. Accurate…
Multiple-image super-resolution of cryo-electron micrographs based on deep internal learning 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, however, result in images where the power of the noise is 100 times greater than the power of…
Accurate size-based protein localization from cryo-ET tomograms Cryo-electron tomography (cryo-ET) combined with sub-tomogram averaging (STA) allows the determination of protein structures imaged within the native context of the cell at near-atomic resolution. Particle picking is an essential step in the cryo-ET/STA image analysis pipeline that consists in locating the position of proteins within crowded cellular tomograms so that they…
Advances in cryo-ET data processing: meeting the demands of visual proteomics 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 collection procedures have seen innovations which enable rapid collection of the large datasets…
Structures of trehalose-6-phosphate synthase, Tps1, from the fungal pathogen Cryptococcus neoformans: A target for antifungals 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 are absent from humans. One…
