Publication highlights

SAMHD1 is a multi-subunit enzyme that regulates the levels of DNA building blocks in the cell, restricts HIV-1 infection of macrophage and resting T-cells, and has roles in cancer and autoimmune disease. Researchers at the Crick conducted time-resolved cryo-EM imaging to directly visualise this enzyme in action. The study captured SAMHD1 over the assembly, steady-state, and substrate-depleted phases of its catalytic process. The imaging shows how dynamic regulatory domains control substrate access and product release from a stable catalytic core. This direct visualisation provides an unprecedented understanding of the dynamics and regulation of a multi-subunit enzyme.

A team led by the Cherepanov lab has found a molecule that can block the binding of a subset of human antibodies to SARS-CoV-2. This could explain patients who, despite having high levels of antibodies, become ill.

We have been able to apply the knowledge we have gained from our work on the infectivity of the influenza virus to the challenge presented by the recent SARS-CoV-2 virus outbreak. In this paper we present high resolution cryo EM structures of the SARS-CoV-2 and bat RaTG13 spike glycoproteins. We describe from a structural perspective the significant differences between the strains. We draw particular attention to the addition of a furin cleavage site into the human virus spike protein. We discuss its potential role in infectivity and on the evolution of this virulent strain.

Here we describe the conformational changes that the SARS-Cov2 spike protein undergoes in binding to the human ACE2 receptor. This represents the initial stages of the mechanism of cell invasion by the virus particle during infection. We show a series of ten cryoEM reconstructions of the spike protein binding to ACE2 through its receptor binding domain (RBD), ranging from a closed unbound spike ectodomain trimer to the fully open conformation with each RBD in the trimer bound to an ACE2 receptor. Binding to ACE2 releases the so-called fusion peptide segment and promotes membrane fusion leading to cell invasion.

Here we determined the structure by single particle cryo-EM of capsid assembly in an endogenous retrovirus. This is the first atomic resolution structure of a closed capsid shell, which in retroviruses packages and protects the genome. By studying 4 different types of symmetric assemblies, we discovered how the underlying Fullerene geometry is achieved by the CA protein forming both pentamers and hexamers and found structural rules by which invariant pentamers and structurally plastic hexamers associate to form the unique polyhedral structures.

The influenza HA is one of two glycoproteins on the surface of influenza virus and mediates receptor binding and membrane fusion during viral entry.In order to understand the function of HA in influenza infectivity it is necessary to understand the mechanism of endocytosis. It has previously been established that endocytosis involves a large conformational rearrangement of the HA protein that can be triggered by a change in pH, revealed by structures of initial and final states. Here, we directly image structural transformations in the HA at the pH of membrane fusion and solve the structure of three structural intermediates including a 150 Å-long triple-helical coiled coil of the HA2 transmembrane subunit. This was a long sought-after result and showed new, surprising concerted conformational rearrangements important to the membrane fusion mechanism.