Taylor lab Macromolecular Structure Laboratory
: Areas of interest
Introduction
In order to prevent, combat or repair defects that lead to disease it is vital that we understand how the macromolecular components of molecular machines assemble, function and co-operate with one another in order to carry out complex biological processes.
To understand how molecular machines function and perform their biological task we study molecular assemblies by applying structural, biophysical and biochemical methodologies. These approaches allow us to dissect a macromolecular complex, visualise the components and examine the interactions between the molecules that make up the complex. Current projects include analysis of the retroviral capsid assembly and the interaction with host factors (Ball et al 2016; Goldstone et al, 2014) and structural studies of host-cell anti retroviral restriction factors and retroviral accessory proteins (Goldstone et al, 2011; Schwefel et al 2014; Arnold et al, 2015).
Research projects
- Macromolecular assemblies in transcriptional 3'-end processing
- Retroviral capsid assembly
- Mechanism of post-entry retroviral restriction factors
- Retroviral accessory proteins
Image layout
The RNA binding domain from the 3’-end processing factor Rna15 bound to either a G (Left) or U (Right) ribonucleotide. The structures reveal an unexpected and conserved GU base selectivity mechanism employed by 3'-end processing complexes to interact with sequence elements at 3'-end of genes.
The structure of the RELIK capsid bound to the host cell factor CypA. The RELIK-CypA complex is shown in cartoon representation on the left, RELIK in blue, CypA in green. Details of the RELIK-CypA molecular interface are shown on the right. This structure and combined virological studies of prehistoric lentiviruses revealed the nature of the evolutionary conserved interaction of retroviruses with the host cell protein cyclophilin-A.
The structure of the HIV-1 restriction factor SAMHD1 with bound dGTP. The SAMHD1 dimer is shown on the left. Individual monomers coloured in magenta and gold and two bound dGTP molecules are shown in stick representation. The molecular details of the linkage between the allosteric and active sites are shown on the right. The structure and combined biochemical studies provides the basis for SAMHD1 inhibition of HIV-1 infection of dendritic cells and macrophages.
