Structural insights into Met receptor activation.
The receptor tyrosine kinase Met plays a pivotal role in vertebrate development and tissue regeneration, its deregulation contributes to cancer. Met is also targeted during the infection by the facultative intracellular bacterium Listeria monocytogenes. The mechanistic basis for Met activation by its natural ligand hepatocyte growth factor/scatter factor (HGF/SF) is only beginning to be understood at a structural level. Crystal structures of Met in complex with L. monocytogenes InlB suggest that Met dimerization by this bacterial invasion protein is mediated by a dimer contact of the ligand. Here, I review the structural basis of Met activation by InlB and highlight parallels and differences to the physiological Met ligand HGF/SF and its splice variant NK1.
Department of Chemistry, Bielefeld University, Universitätsstrasse 25, 33615 Bielefeld, Germany. Hartmut.Niemann@uni-bielefeld.de
Hartmut H
HH
Niemann
D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism; D002454:Cell Differentiation; D017228:Hepatocyte Growth Factor / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008024:Ligands; D008089:Listeria monocytogenes / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D011485:Protein Binding; D055503:Protein Multimerization; D019859:Proto-Oncogene Proteins c-met / Q000737:chemistry* / Q000378:metabolism*
D001426:Bacterial Proteins; D008024:Ligands; D008565:Membrane Proteins; C095768:inlB protein, Listeria monocytogenes; D017228:Hepatocyte Growth Factor; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met