STructures of two Ig-like domains of intimin solved

Enteropathogenic and enterohaemorrhagic Escherichia coli (EPEC and EHEC, respectively) are major causes of diarrhoeal disease. To cause disease, EPEC and EHEC must bind to the cells of the intestine. This causes rearrangements of the cell surface, resulting in a “pedestal” around the bacteria. The formation of this structure is necessary for intimate attachment of the bacteria to intestinal cells, which in turn is necessary for diarrhoea to develop.

Pedestal formation depends on a surface protein called intimin, which is an adhesin that mediates the intimate attachment of the pathogens to the intestinal cells. The adhesive tip of intimin is projected away from the bacterial surface by several tandemly arranged immunoglobulin (Ig)-like domains that form the “stalk” of the protein.

Jack C. Leo and colleagues from Denmark, Norway, Sweden, Germany and Japan have solved the structure of two of the Ig-like domains, called D00 and D0, which are located at the beginning of the stalk. These have been the final missing pieces which allow full structural modelling of the extracellular region of intimin. The short connector between these two domains is rigid, whereas the connectors between the other Ig-like domains are more flexible. Using computer modelling, the researchers show that this arrangement of rigid and flexible regions increases the overall reach of the adhesin, i.e. allows it to project further on average from the bacterial surface than if all the connectors were flexible. The flexibility of some parts, on the other hand, could help the adhesin bind to its receptor on the host cell surface. 

Weikum J, Kulakova A, Tesei G., et al. The extracellular juncture domains in the intimin passenger adopt a constitutively extended conformation inducing restraints to its sphere of action. Sci Rep. 2020; doi.org/10.1038/s41598-020-77706-7.