Jeremy Tame

My group focuses on biophysical studies of how proteins fold and function. The principal techniques used are protein crystallography, analytical ultracentrifugation and isothermal titration calorimetry. We have a well-equipped laboratory for manipulation of DNA, protein expression and crystallisation, and we have published extensively in both general science journals and more specialist biochemistry publications.

My publication list is available here.
My book Approaches to Entropy is available from Springer here.

After I graduated from Cambridge University in England, I moved down the road to the MRC Laboratory of Molecular Biology. Following a short period of funding arranged by the Nobel prize winner Max Perutz, I became a regular student in the group of Kiyoshi Nagai, who was working on methods to create site-directed mutants of human haemoglobin, a protein that proved highly difficult to express in bacteria at that time. My PhD thesis involved the first mutational studies of the alpha subunit of human haemoglobin, showing its behaviour is very different from the beta subunit, and I still have enormous interest in haemoglobin as a test-bed for protein structure-function studies, as well as a wonderful opportunity to observe evolution on the molecular level. My group refined the crystal structure of haemoglobin to atomic resolution, in both the oxy and deoxy states, greatly clarifying the nature of the interactions between the protein and the diatomic ligand. This work has been widely cited by groups working in diverse fields from allostery to molecular dynamics simulations. We have also studied a variety of animal haemoglobins showing that evolution has created very different mechanisms for regulating the oxygen affinity of the protein. Many fish, for example, use Hb to drive oxygen into the swim-bladder against a strong concentration gradient. We have shown that very different residues at different positions on the protein may be used to create extremely pH-sensitive oxygen affinity effects. Crocodiles have a unique mechanism of exploiting bicarbonate ions to drive oxygen off their haemoglobin, and my PhD thesis helped establish the site of bicarbonate binding. My group has crystallised a variant of human haemoglobin with the same binding site engineered into it, showing that the protein can adopt a completely new structure not seen in any other vertebrate haemoglobin.

Protein design
Recently my group has collaborated with Prof. Arnout Voet at KU Leuven to produce novel proteins with perfect Cn symmetry. The first of these designs, called Pizza, was a beta-propeller protein with six-fold symmetry. This protein showed that a single polypeptide chain with a number of domains of identical sequence can still fold properly, contrary to some ideas that such a protein would suffer "folding frustration" as the domains interfered with each other, leading to a misfolded aggregate. We have used Pizza to create a miniature crystal of cadmium chloride with only 19 atoms, and we are now building on this work to make templates to form metallic nano-clusters with uses in a variety of fields including medicine and biotechnology. The basic design model, of a propeller protein with six blades of identical sequence, can be found at PDB here: 3WW9. The paper describing the protein and its design can be found via Pubmed here.

Anti-cancer lectins
My group has solved the structure of a novel lectin called MytiLec, isolated from the edible mussel, Mytillus galloprovincialis. This protein has a beta-trefoil structure, and a novel form of sugar-binding site. This protein targets particular types of cancerous cell that express globotriose on the cell surface. By binding to galactose residues, Mytilec recognises these cells, and by unknown means enters them and kills them. The high-resolution structures solved by our group showed that the interactions between the protein and ligand are unlike those of previously solved lectin structures. The crystal structure can be downloaded from the PDB at 3WMV. The paper describing the protein and its sugar binding can be found via Pubmed here.

Thermodynamics of protein-ligand binding
I have a long-standing interest in protein thermodynamics, starting with haemoglobin, but also including sugars, peptides and small molecule drugs. I have been invited to speak at a variety of meetings on this topic, and my work on the peptide-binding protein OppA has proved very popular as a system to test ideas on relating protein structures and ligand binding energies. My work on OppA in the 1990s was the first attempt to relate a number of crystal structures of a protein bound to several different ligands, and the ligand affinity measured by calorimetry. A freely available paper describing the crystallographic and thermodynamic analyis of several OppA complexes can be found via Pubmed here.
Two commentaries of mine on the calculation of ligand affinity from static protein crystallographic models have been highly cited, the first, published in 1999, pointed out that many algorithms were highly simplistic and unlikely to work reliably and generally. The second shows that there is no thermodynamic basis for believing that separate entropic and enthalpic terms can be calculated even approximately from static, desolvated models. The two papers can be downloaded here and here.

If you would like to contact me or my group, please find the relevant information on the Contact page.

Latest Updates

September, 2019: We were devastated to learn of the sad death of Kiyoshi Nagai, who has passed away from liver cancer in Cambridge. You can learn a little more about this truly wonderful man here.
April, 2021: I served as Editor for Biophysical Reviews, and was requested to provide a short autobiographical piece, which is free to download: https://link.springer.com/article/10.1007/s12551-021-00798-6
November, 2023: I was delighted to be invited to speak at a memorial meeting, to be held at the MRC LMB in Cambridge, commemorating the life and work of Kiyoshi Nagai and Chris Oubridge.