PMID- 23123275
OWN - NLM
STAT- MEDLINE
DCOM- 20131107
LR  - 20161126
IS  - 0006-3002 (Print)
IS  - 0006-3002 (Linking)
VI  - 1834
IP  - 10
DP  - 2013 Oct
TI  - Structural basis of MET receptor dimerization by the bacterial invasion protein 
      InlB and the HGF/SF splice variant NK1.
PG  - 2195-204
LID - S1570-9639(12)00253-1 [pii]
LID - 10.1016/j.bbapap.2012.10.012 [doi]
AB  - The structural basis of ligand-induced dimerization of the receptor tyrosine 
      kinase MET by its natural ligand hepatocyte growth factor/scatter factor (HGF/SF) 
      is not well understood. However, interesting insight into the molecular mechanism 
      of MET dimerization has emerged from crystal structures of MET in complex with a 
      bacterial agonist, the invasion protein internalin B (InlB) from pathogenic 
      Listeria monocytogenes. MET activation by InlB promotes uptake of bacteria into 
      host cells. Structural and biophysical data suggest that InlB is monomeric on its 
      own but dimerizes upon binding to the membrane-anchored MET receptor promoting 
      the formation of a signaling active 2:2 complex. The dimerization interface is 
      small and unusually located on the convex side of the curved InlB leucine-rich 
      repeat (LRR) domain. As InlB does not dimerize in solution, the dimerization site 
      could only be identified by studying packing contacts of InlB in various crystal 
      forms and had to be proven by scrutinizing its biological relevance in cellular 
      assays. InlB dimerization is thus an example of a low-affinity contact that 
      appears irrelevant in solution but becomes physiologically significant in the 
      context of 2-dimensional diffusion restricted to the membrane plane. The 
      resulting 2:2 InlB:MET complex has an InlB dimer at its center with one MET 
      molecule bound peripherally to each InlB. This model of ligand-mediated MET 
      dimerization may serve as a blue-print to understand MET activation by NK1, a 
      naturally occurring HGF/SF splice variant and MET agonist. Crystal structures of 
      NK1 repeatedly show a NK1 dimer, in which residues implicated in MET-binding are 
      located on the outside. Thus, MET dimerization by NK1 may also be ligand-mediated 
      with a NK1 dimer at the center of the 2:2 complex with one MET molecule bound 
      peripherally to each NK1. This article is part of a Special Issue entitled: 
      Emerging recognition and activation mechanisms of receptor tyrosine kinases.
CI  - Copyright (c) 2012 Elsevier B.V. All rights reserved.
FAU - Niemann, Hartmut H
AU  - Niemann HH
AD  - Department of Chemistry and Center for Biotechnology (CeBiTec), Bielefeld 
      University, 33501 Bielefeld, Germany. Electronic address: 
      Hartmut.Niemann@uni-bielefeld.de.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20121031
PL  - Netherlands
TA  - Biochim Biophys Acta
JT  - Biochimica et biophysica acta
JID - 0217513
RN  - 0 (Bacterial Proteins)
RN  - 0 (HGF protein, human)
RN  - 0 (Ligands)
RN  - 0 (Membrane Proteins)
RN  - 0 (Protein Isoforms)
RN  - 0 (inlB protein, Listeria monocytogenes)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
RN  - EC 2.7.10.1 (MET protein, human)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-met)
SB  - IM
MH  - Alternative Splicing
MH  - Bacterial Proteins/*chemistry/genetics/metabolism
MH  - Binding Sites
MH  - Epithelial Cells/cytology/metabolism
MH  - Gene Expression Regulation
MH  - Hepatocyte Growth Factor/*chemistry/genetics/metabolism
MH  - Humans
MH  - Ligands
MH  - Membrane Proteins/*chemistry/genetics/metabolism
MH  - Models, Molecular
MH  - Protein Binding
MH  - Protein Isoforms/chemistry/genetics/metabolism
MH  - Protein Multimerization
MH  - Proto-Oncogene Proteins c-met/*chemistry/genetics/metabolism
MH  - Signal Transduction
OTO - NOTNLM
OT  - HGF/SF
OT  - Hepatocyte growth factor/scatter factor
OT  - InlB
OT  - Internalin
OT  - Receptor tyrosine kinase
OT  - c-MET
EDAT- 2012/11/06 06:00
MHDA- 2013/11/08 06:00
CRDT- 2012/11/06 06:00
PHST- 2012/09/04 00:00 [received]
PHST- 2012/10/19 00:00 [revised]
PHST- 2012/10/23 00:00 [accepted]
PHST- 2012/11/06 06:00 [entrez]
PHST- 2012/11/06 06:00 [pubmed]
PHST- 2013/11/08 06:00 [medline]
AID - S1570-9639(12)00253-1 [pii]
AID - 10.1016/j.bbapap.2012.10.012 [doi]
PST - ppublish
SO  - Biochim Biophys Acta. 2013 Oct;1834(10):2195-204. doi: 
      10.1016/j.bbapap.2012.10.012. Epub 2012 Oct 31.