The facultative intracellular human pathogen L. monocytogenes
produces a distinct number of virulence factors, that usually mimic host cell processes leading e.g. to invasion and propagation within the host. In the past we have determined the high resolution crystal structures of internalins and internalin-like proteins
from L. monocytogenes
. Common to all these proteins is the presence of a so-called leucine-rich repeat (LRR) domain that specifically interacts with host cell receptors during invasion. The structure of the complex between the receptor-binding domain of internalin A
and the N-terminal domain of human E-cadherin (Schubert, 2002)
provided a detailed picture of the first step of listerial infection in the human intestine. It also explained the known host tropism of L. monocytogenes
towards humans but not mice. For further information and follow-up projects see this link.
Recently we have solved the structure of the complex between second listerial invasion protein InlB with its human receptor Met
, the natural tyrosine kinase receptor of hepatocyte growth factor/scatter factor (HGF/SF), which initiates uptake of the bacteria by many different tissues. The structure shows that InlB predominantly interacts via its LRR-domain with the Ig1-domain of Met in constrast to HGF/SF which targets the N-terminal Sema-domain (Niemann, 2007
). We are currently investigating how the InlB-Met-interaction leads to uptake of the bacteria by the host.