Only three amino acids, building blocks of a certain bacterial molecule, account for the firm connection between bacterium and intestinal cell.
Every year infections with EHEC keep researchers in industrialised countries busy. During an infection the bacteria colonize the intestinal mucosa and produce a toxin that causes bloody diarrhoea, leading to severe complications.
"EHEC are pathogenic relatives of E. coli bacteria that are part of our healthy intestinal flora," says Professor Theresia Stradal who recently changed from the HZI to the University of Münster. EHEC enter our body mainly via contaminated food. Within the body they tightly bind to the surface of intestinal cells. "Doing so, they inject a protein cocktail via a 'molecular syringe' into the host cell, initiating a so-called signal cascade." In the course of these processes, the bacteria firmly anchor on the surface of the intestinal cell, sitting on a small pedestal formed by the host’s cytoskeleton. Production of the diarrhoea causing toxin is independent of these processes.
The stable contact between EHEC and intestinal cell is mediated through three proteins – the bacterial factors Tir and EspFU that are being translocated into the host cell, and IRSp53 of the intestinal cell. The latter accumulates beneath the bacterium at the inner cell surface, bridging to host cell proteins that initiate and maintain pedestal formation.
Structural biologists of the HZI have now deciphered the interaction between the EHEC factor Tir and the human protein IRSp53. They analysed the atomic structure of both proteins during their interaction and discovered that two Tir proteins and a single two-chain IRSp53 bind in a key-lock fashion. Notably, just three amino acids of the bacterial protein Tir are essential to mediate this firm interaction, fitting in a newly discovered binding groove on the surface of the host protein IRSp53. "The stability and specificity was very surprising to us," explains Doctor Konrad Büssow, of the HZI.
The change of just one single amino acid on either the bacterial Tir or human IRSp53 already weakened or even abrogated binding of the two proteins. "This work unveils for the first time atomic details of this interaction between EHEC Tir and host IRSp53," says Büssow.
MEDICA.de; Source: Helmholtz Centre for Infection Research