Signal strapping—a proteomic search technique for the discovery of metalloproteins

Thursday January 15th at 11 am
Department of Chemistry of ENS, Salle R
24, rue Lhomond, 75005 Paris

Paul H. Walton, Joao Cairo, Gideon Davies
Department of Chemistry, University of York, Heslington, York, UK, YO10 5DD
paul.walton@york.ac.uk

The discovery of the histidine brace active site in 2010, opened-up a new avenue of research into copper oxygenases and their model complexes.[1] The former includes enzymes such as particulate methane monooxygenase and lytic polysaccharide monooxygenases. The latter has given rise to new types of copper oxidation catalysts. The histidine brace active site is characterized by an N-terminal histidine residue acting as a chelate to a single copper ion. On this basis, we hypothesized that any protein sequence with an N-terminal histidine would be a metalloprotein, and that—if the protein sequence was one of unknown function—that the resulting metalloprotein may have new types of activity.

I present here the method of signal strapping, which is a proteomic search method which can be used to find new N-terminal histidine metalloproteins. Using this method, we have discovered several new metalloproteins, all of which have previously undescribed functions.         In this talk, I will exemplify the approach with the description of the discovery of new metal transport proteins, including a new class of proteins, called anglerases, which are capable of ‘fishing’ metal ions from the surrounding milieu of bacteria.

Depiction of closed (left) and open (right) form of an anglerase:

• H. Walton, G. J. Davies, Daniel, E. Diaz, Joao P Franco-Cairo, FEBS Lett, 2023, 1873.

Paul Walton’s main research area is bioinorganic chemistry, in which he has made contributions to the understanding of copper oxidases, including the discovery of the histidine brace, the bioinformatic method of signal-strapping and anglerase metalloproteins. Paul is an internationally-known advocate of equality in sciences and lectures widely on the subject and will give a conference on Bram Day, Friday Jan. 16th.