TY  - JOUR
A1  - Ebbes, Maria
A1  - Bleymüller, Willem M.
A1  - Cernescu, Mihaela
A1  - Nölker, Rolf
A1  - Brutschy, Bernd
A1  - Niemann, Hartmut H.
T1  - Fold and function of the InlB B-repeat
T2  - Journal of biological chemistry
N2  - Host cell invasion by the facultative intracellular pathogen Listeria monocytogenes requires the invasion protein InlB in many cell types. InlB consists of an N-terminal internalin domain that binds the host cell receptor tyrosine kinase Met and C-terminal GW domains that bind to glycosaminoglycans (GAGs). Met binding and activation is required for host cell invasion, while the interaction between GW domains and GAGs enhances this effect. Soluble InlB elicits the same cellular phenotypes as the natural Met ligand hepatocyte growth factor/scatter factor (HGF/SF), e.g. cell scatter. So far, little is known about the central part of InlB, the B-repeat. Here we present a structural and functional characterization of the InlB B-repeat. The crystal structure reveals a variation of the β-grasp fold that is most similar to small ubiquitin-like modifiers (SUMOs). However, structural similarity also suggests a potential evolutionary relation to bacterial mucin-binding proteins. The B-repeat defines the prototype structure of a hitherto uncharacterized domain present in over a thousand bacterial proteins. Generally, this domain probably acts as a spacer or a receptor-binding domain in extracellular multi-domain proteins. In cellular assays the B-repeat acts synergistically with the internalin domain conferring to it the ability to stimulate cell motility. Thus, the B-repeat probably binds a further host cell receptor and thereby enhances signaling downstream of Met.
KW  - Adhesion
KW  - Bacteria
KW  - Cell Surface Receptor
KW  - Crystal Structure
KW  - Evolution
KW  - Protein Domains
KW  - Protein Structure
KW  - Receptor Tyrosine Kinase
KW  - Signal Transduction
KW  - X-ray Crystallography
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/76598
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-765982
SN  - 0021-9258
VL  - 286.2011
IS  - 17
SP  - 15496
EP  - 15506
PB  - American Society for Biochemistry and Molecular Biology Publications
CY  - Bethesda, Md
ER  -