Ian Taylor

Macromolecular Structure Laboratory

Many of the fundamental processes carried out within living cells are directed by macromolecular assemblies of protein and nucleic acid molecules, often referred to as 'molecular machines'. Malfunction of a molecular machine resulting in the breakdown of a normal cellular process is the cause of many human cancers, developmental defects, neurological disorders and other congenital disease states. 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 examining complexes that mediate transcriptional elongation, 3'-end processing and polyadenylation (Pancevac et al, 2010) analysis of the interaction of the retroviral capsid with host factors (Hilditch et al, 2011; Goldstone et al, 2014) and structural studies of host-cell anti retroviral restriction factors (Goldstone et al, 2011; Schwefel et al 2014).

Figure 1

Figure 1. 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. (Click to view larger image)

Figure 2

Figure 2. 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. (Click to view larger image)

Figure 3

Figure 3. 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. (Click to view larger image)


Research projects

  • Macromolecular assemblies in transcriptional 3'-end processing
  • Retroviral capsid assembly
  • Mechanism of post-entry retroviral restriction factors
  • Retroviral accessory proteins

Selected publications

Goldstone DC, Walker PA, Calder L, Coombs, PJ, Kirkpatrick J, Ball NJ, Hilditch L, Yap MW, Rosenthal PB, Stoye JP, Taylor IA. (2014). Structural studies of postentry restriction factors reveal antiparallel dimers that enable avid binding to the HIV-1 capsid lattice. Proc Natl Acad Sci U S A 111(26): 9609-9614

Schwefel D, Groom HCT, Boucherit VC, Christodoulou E, Walker PA, Stoye JP, Bishop KN, Taylor IA (2014). Structural basis of lentiviral subversion of a cellular protein degradation pathway. Nature 505: 234-238

Goldstone DC, Flower TG, Ball NJ, Sanz-Ramos M, Yap MW, Ogrodowicz RW, Stanke N, Reh J, Lindemann D, Stoye JP, Taylor IA (2013). A Unique Spumavirus Gag N-terminal Domain with Functional Properties of Orthoretroviral Matrix and Capsid. PLoS pathogens 9: e1003376

Goldstone, DC; Ennis-Adeniran, V; Hedden, JJ; Groom, HCT; Rice, GI; Christodoulou, E; Walker, PA; Kelly, G; Haire, LF; Yap, MW; de Carvalho, LP; Stoye, JP; Crow, YJ; Taylor, IA and Webb, M (2011) HIV-1 restriction factor SAMHD1 is a deoxynucleoside triphosphate triphosphohydrolase. Nature 480, 379-382

Hilditch, L; Matadeen, R; Goldstone, DC; Rosenthal, PB; Taylor, IA and Stoye, JP (2011) Ordered assembly of murine leukemia virus capsid protein on lipid nanotubes directs specific binding by the restriction factor, Fv1. Proceedings of the National Academy of Sciences of the United States of America 108, 5771-5776

Goldstone, DC; Yap, MW; Robertson, LE; Haire, LF; Taylor, WR; Katzourakis, A; Stoye, JP and Taylor, IA (2010) Structural and functional analysis of prehistoric lentiviruses uncovers an ancient molecular interface. Cell Host & Microbe 8, 248-259

Pancevac, C; Goldstone, DC; Ramos, A and Taylor, IA (2010) Structure of the Rna15 RRM-RNA complex reveals the molecular basis of GU specificity in transcriptional 3'-end processing factors. Nucleic Acids Research 38, 3119-3132

Ian Taylor

ian.taylor@crick.ac.uk
+44 (0)20 379 62288

  • Qualifications and history
  • 1993 PhD, SERC University of Portsmouth, UK
  • 1994 Post doctoral fellow Medical Research Council National Institute for Medical Research (MRC-NIMR), London, UK
  • 1999 Post doctoral fellow University of Oxford, UK
  • 2001 Group Leader, MRC-NIMR, London, UK
  • 2015 Group Leader, the Francis Crick Institute, London, UK