Data Collection to Structure Refinement and Beyond
Retroviruses and other RNA viruses translate key proteins from a single mRNA relying on translational frameshift to produce concatenating protein domains called polyproteins before subsequent cleavage during maturation to produce mature and highly functional proteins. For HIV, a single mRNA is used to produce precursor structural polyproteins (Gag) and Gag-Pol which contains both the structural…
A comprehensive understanding of the molecular architecture of the slit diaphragm (SD), a critical component of the glomerular filtration barrier, is essential in elucidating renal filtration physiology and the mechanisms underlying kidney disease. Disruption of the SD is a hallmark of all forms of glomerulopathies, regardless of whether the cause is genetic, immunological, metabolic, or…
Mycoplasma pneumoniae, responsible for approximately 30% of community-acquired human pneumonia, needs to extract lipids from the host environment for survival and proliferation. A comprehensive structural and functional analysis of the protein P116 by single-particle cryo-electron microscopy reveals a homodimer presenting a previously unseen fold, forming a huge hydrophobic cavity, which is fully accessible to solvent.…
Discover how STEM-evolved monoclonal antibodies outpaced SARS-CoV-2 variants, revealed by cryo-EM structural insights.
The mission of the Chan Zuckerberg Imaging Institute (CZII) is to enable deep insights into the architecture of complex biological systems at the molecular level, through the development and application of novel imaging technologies. The initial grand challenge for CZII is to develop technologies and methodologies to image the molecular architecture of the cell to…
Electron cryomicroscopy can, in principle, determine the structures of most biological molecules, but is currently limited by access, specimen preparation difficulties and cost. We present a purpose-built instrument operating at 100 keV (instead of the widely-used 300 keV instruments) – including advances in electron optics, detection and processing – that makes structure determination fast and…
Angiotensin-converting enzyme (ACE) is a zinc metallopeptidase that plays a critical role in blood pressure, and fluid and electrolyte homeostasis. ACE can cleave angiotensin I, bradykinin, and many other peptide substrates. Until recently, little was known regarding the specific role of each of the two ACE domains, their 3D structural orientation, dynamics and dimerization. In…
The electron Bio-Imaging Centre (eBIC) at Diamond Light Source offers a unique service to pharma and biotech companies to rapidly advance their discovery and development of lead compounds, biologics, or drug carriers whilst uncovering valuable information regarding biomolecule structure, stability and domain flexibility by using cryo-EM. By offering flexible access to world class cryo-EM facilities,…
The atomic structure of insulin has been known since the late 1960s, but it is only relatively recently that molecular detail has been obtained of the insulin receptor and of the way in which insulin and its receptor interact and effect signal transduction into the cellular interior. These advances have been dependent both on the…
Single-particle cryo-EM, in being able to capture an entire spectrum of states of a biomolecular complex, is uniquely suited for drug discovery as well as development of vaccines. Increasingly the capacity of a biomolecule to “breathe” and change its structure dynamically in the thermal bath is recognized as key in understanding drug efficacy and, more…