MET-activating Residues in the B-repeat of theListeria monocytogenesInvasion Protein InlB

Bleymüller W, Lämmermann N, Ebbes M, Maynard D, Geerds C, Niemann H (2016)
Journal of Biological Chemistry 291(49): 25567-25577.

Zeitschriftenaufsatz | Veröffentlicht | Englisch
Es wurden keine Dateien hochgeladen. Nur Publikationsnachweis!
Abstract / Bemerkung
The facultative intracellular pathogen Listeria monocytogenes causes listeriosis, a rare but life-threatening disease. Host cell entry begins with activation of the human receptor tyrosine kinase MET through the bacterial invasion protein InlB, which contains an internalin domain, a B-repeat, and three GW domains. The internalin domain is known to bind MET, but no interaction partner is known for the B-repeat. Adding the B-repeat to the internalin domain potentiates MET activation and is required to stimulate Madin Darbey canine kidney (MDCK) cell scatter. Therefore, it has been hypothesized that the B-repeat may bind a co-receptor on host cells. To test this hypothesis, we mutated residues that might be important for binding an interaction partner. We identified two adjacent residues in strand beta2 of the beta-grasp fold whose mutation abrogated induction of MDCK cell scatter. Biophysical analysis indicated that these mutations do not alter protein structure. We then tested these mutants in human HT-29 cells which, in contrast to the MDCK cells, were responsive to the internalin domain alone. These assays revealed a dominant negative effect, reducing the activity of a construct of the internalin domain and mutated B-repeat below that of the individual internalin domain. Phosphorylation assays of MET and its downstream targets AKT and ERK confirmed the dominant negative effect. Attempts to identify a host cell receptor for the B-repeat were not successful. We conclude that there is limited support for a co-receptor hypothesis, and instead suggest that the B-repeat contributes to MET activation through low-affinity homodimerization. Copyright 2016, The American Society for Biochemistry and Molecular Biology.
cell signaling; cell surface receptor; dimerization; growth factor; protein domain; protein structure; protein-protein interaction; receptor tyrosine kinase; signal transduction; structure-function
Journal of Biological Chemistry
0021-9258, 1083-351X
Page URI


Bleymüller W, Lämmermann N, Ebbes M, Maynard D, Geerds C, Niemann H. MET-activating Residues in the B-repeat of theListeria monocytogenesInvasion Protein InlB. Journal of Biological Chemistry. 2016;291(49):25567-25577.
Bleymüller, W., Lämmermann, N., Ebbes, M., Maynard, D., Geerds, C., & Niemann, H. (2016). MET-activating Residues in the B-repeat of theListeria monocytogenesInvasion Protein InlB. Journal of Biological Chemistry, 291(49), 25567-25577. doi:10.1074/jbc.m116.746685
Bleymüller, W., Lämmermann, N., Ebbes, M., Maynard, D., Geerds, C., and Niemann, H. (2016). MET-activating Residues in the B-repeat of theListeria monocytogenesInvasion Protein InlB. Journal of Biological Chemistry 291, 25567-25577.
Bleymüller, W., et al., 2016. MET-activating Residues in the B-repeat of theListeria monocytogenesInvasion Protein InlB. Journal of Biological Chemistry, 291(49), p 25567-25577.
W. Bleymüller, et al., “MET-activating Residues in the B-repeat of theListeria monocytogenesInvasion Protein InlB”, Journal of Biological Chemistry, vol. 291, 2016, pp. 25567-25577.
Bleymüller, W., Lämmermann, N., Ebbes, M., Maynard, D., Geerds, C., Niemann, H.: MET-activating Residues in the B-repeat of theListeria monocytogenesInvasion Protein InlB. Journal of Biological Chemistry. 291, 25567-25577 (2016).
Bleymüller, Willem, Lämmermann, Nina, Ebbes, Maria, Maynard, Daniel, Geerds, Christina, and Niemann, Hartmut. “MET-activating Residues in the B-repeat of theListeria monocytogenesInvasion Protein InlB”. Journal of Biological Chemistry 291.49 (2016): 25567-25577.

1 Zitation in Europe PMC

Daten bereitgestellt von Europe PubMed Central.

61 References

Daten bereitgestellt von Europe PubMed Central.

Listeriosis: a resurgent foodborne infection.
Allerberger F, Wagner M., Clin. Microbiol. Infect. 16(1), 2010
PMID: 20002687
The InIB protein of Listeria monocytogenes is sufficient to promote entry into mammalian cells.
Braun L, Ohayon H, Cossart P., Mol. Microbiol. 27(5), 1998
PMID: 9535096
InIB-dependent internalization of Listeria is mediated by the Met receptor tyrosine kinase.
Shen Y, Naujokas M, Park M, Ireton K., Cell 103(3), 2000
PMID: 11081636
Met, metastasis, motility and more.
Birchmeier C, Birchmeier W, Gherardi E, Vande Woude GF., Nat. Rev. Mol. Cell Biol. 4(12), 2003
PMID: 14685170
Multiple regions of internalin B contribute to its ability to turn on the Ras-mitogen-activated protein kinase pathway.
Copp J, Marino M, Banerjee M, Ghosh P, van der Geer P., J. Biol. Chem. 278(10), 2002
PMID: 12488439
Internalins: a complex family of leucine-rich repeat-containing proteins in Listeria monocytogenes.
Bierne H, Sabet C, Personnic N, Cossart P., Microbes Infect. 9(10), 2007
PMID: 17764999
The leucine-rich repeat: a versatile binding motif.
Kobe B, Deisenhofer J., Trends Biochem. Sci. 19(10), 1994
PMID: 7817399
Structure of the human receptor tyrosine kinase met in complex with the Listeria invasion protein InlB.
Niemann HH, Jager V, Butler PJ, van den Heuvel J, Schmidt S, Ferraris D, Gherardi E, Heinz DW., Cell 130(2), 2007
PMID: 17662939
Ligand-mediated dimerization of the Met receptor tyrosine kinase by the bacterial invasion protein InlB.
Ferraris DM, Gherardi E, Di Y, Heinz DW, Niemann HH., J. Mol. Biol. 395(3), 2009
PMID: 19900460
InlB: an invasion protein of Listeria monocytogenes with a novel type of surface association.
Braun L, Dramsi S, Dehoux P, Bierne H, Lindahl G, Cossart P., Mol. Microbiol. 25(2), 1997
PMID: 9282740
GW domains of the Listeria monocytogenes invasion protein InlB are SH3-like and mediate binding to host ligands.
Marino M, Banerjee M, Jonquieres R, Cossart P, Ghosh P., EMBO J. 21(21), 2002
PMID: 12411480
GW domains of the Listeria monocytogenes invasion protein InlB are required for potentiation of Met activation.
Banerjee M, Copp J, Vuga D, Marino M, Chapman T, van der Geer P, Ghosh P., Mol. Microbiol. 52(1), 2004
PMID: 15049825
Fold and function of the InlB B-repeat.
Ebbes M, Bleymuller WM, Cernescu M, Nolker R, Brutschy B, Niemann HH., J. Biol. Chem. 286(17), 2011
PMID: 21345802
The Pfam protein families database.
Finn RD, Mistry J, Tate J, Coggill P, Heger A, Pollington JE, Gavin OL, Gunasekaran P, Ceric G, Forslund K, Holm L, Sonnhammer EL, Eddy SR, Bateman A., Nucleic Acids Res. 38(Database issue), 2009
PMID: 19920124
Dali server: conservation mapping in 3D.
Holm L, Rosenstrom P., Nucleic Acids Res. 38(Web Server issue), 2010
PMID: 20457744
Comparison of three-dimensional structures of homologous proteins
Overington J.., 1992
Small but versatile: the extraordinary functional and structural diversity of the beta-grasp fold.
Burroughs AM, Balaji S, Iyer LM, Aravind L., Biol. Direct 2(), 2007
PMID: 17605815
Ubiquitin--molecular mechanisms for recognition of different structures.
Perica T, Chothia C., Curr. Opin. Struct. Biol. 20(3), 2010
PMID: 20456943
Structural and functional roles of Daxx SIM phosphorylation in SUMO paralog-selective binding and apoptosis modulation.
Chang CC, Naik MT, Huang YS, Jeng JC, Liao PH, Kuo HY, Ho CC, Hsieh YL, Lin CH, Huang NJ, Naik NM, Kung CC, Lin SY, Chen RH, Chang KS, Huang TH, Shih HM., Mol. Cell 42(1), 2011
PMID: 21474068
Complex between Peptostreptococcus magnus protein L and a human antibody reveals structural convergence in the interaction modes of Fab binding proteins.
Graille M, Stura EA, Housden NG, Beckingham JA, Bottomley SP, Beale D, Taussig MJ, Sutton BJ, Gore MG, Charbonnier JB., Structure 9(8), 2001
PMID: 11587642
Scatter factor is a fibroblast-derived modulator of epithelial cell mobility.
Stoker M, Gherardi E, Perryman M, Gray J., Nature 327(6119), 1987
PMID: 2952888
An epithelial scatter factor released by embryo fibroblasts.
Stoker M, Perryman M., J. Cell. Sci. 77(), 1985
PMID: 3841349
Epithelial-mesenchymal transitions in tumour progression.
Thiery JP., Nat. Rev. Cancer 2(6), 2002
PMID: 12189386
Protein binding site prediction using an empirical scoring function.
Liang S, Zhang C, Liu S, Zhou Y., Nucleic Acids Res. 34(13), 2006
PMID: 16893954
Accurate secondary structure prediction and fold recognition for circular dichroism spectroscopy.
Micsonai A, Wien F, Kernya L, Lee YH, Goto Y, Refregiers M, Kardos J., Proc. Natl. Acad. Sci. U.S.A. 112(24), 2015
PMID: 26038575
Aromatic amino acids at the surface of InlB are essential for host cell invasion by Listeria monocytogenes.
Machner MP, Frese S, Schubert WD, Orian-Rousseau V, Gherardi E, Wehland J, Niemann HH, Heinz DW., Mol. Microbiol. 48(6), 2003
PMID: 12791136
c-Met recruits ICAM-1 as a coreceptor to compensate for the loss of CD44 in Cd44 null mice.
Olaku V, Matzke A, Mitchell C, Hasenauer S, Sakkaravarthi A, Pace G, Ponta H, Orian-Rousseau V., Mol. Biol. Cell 22(15), 2011
PMID: 21680714
Integrin α6β4 Promotes Autocrine Epidermal Growth Factor Receptor (EGFR) Signaling to Stimulate Migration and Invasion toward Hepatocyte Growth Factor (HGF).
Carpenter BL, Chen M, Knifley T, Davis KA, Harrison SM, Stewart RL, O'Connor KL., J. Biol. Chem. 290(45), 2015
PMID: 26381405
Hepatocyte growth factor-induced Ras activation requires ERM proteins linked to both CD44v6 and F-actin.
Orian-Rousseau V, Morrison H, Matzke A, Kastilan T, Pace G, Herrlich P, Ponta H., Mol. Biol. Cell 18(1), 2006
PMID: 17065554
Involvement of CD44v6 in InlB-dependent Listeria invasion.
Jung C, Matzke A, Niemann HH, Schwerk C, Tenenbaum T, Orian-Rousseau V., Mol. Microbiol. 72(5), 2009
PMID: 19432801
Four individually druggable MET hotspots mediate HGF-driven tumor progression.
Basilico C, Hultberg A, Blanchetot C, de Jonge N, Festjens E, Hanssens V, Osepa SI, De Boeck G, Mira A, Cazzanti M, Morello V, Dreier T, Saunders M, de Haard H, Michieli P., J. Clin. Invest. 124(7), 2014
PMID: 24865428
Artificial human Met agonists based on macrocycle scaffolds.
Ito K, Sakai K, Suzuki Y, Ozawa N, Hatta T, Natsume T, Matsumoto K, Suga H., Nat Commun 6(), 2015
PMID: 25758345
Oligonucleotide-Based Mimetics of Hepatocyte Growth Factor.
Ueki R, Ueki A, Kanda N, Sando S., Angew. Chem. Int. Ed. Engl. 55(2), 2015
PMID: 26592704
Structure, domain organization, and different conformational states of stem cell factor-induced intact KIT dimers.
Opatowsky Y, Lax I, Tome F, Bleichert F, Unger VM, Schlessinger J., Proc. Natl. Acad. Sci. U.S.A. 111(5), 2014
PMID: 24449920
The strength and cooperativity of KIT ectodomain contacts determine normal ligand-dependent stimulation or oncogenic activation in cancer.
Reshetnyak AV, Opatowsky Y, Boggon TJ, Folta-Stogniew E, Tome F, Lax I, Schlessinger J., Mol. Cell 57(1), 2014
PMID: 25544564
Structural basis for activation of the receptor tyrosine kinase KIT by stem cell factor.
Yuzawa S, Opatowsky Y, Zhang Z, Mandiyan V, Lax I, Schlessinger J., Cell 130(2), 2007
PMID: 17662946
Single-molecule photobleaching reveals increased MET receptor dimerization upon ligand binding in intact cells.
Dietz MS, Haße D, Ferraris DM, Gohler A, Niemann HH, Heilemann M., BMC Biophys 6(1), 2013
PMID: 23731667
Live cell imaging shows hepatocyte growth factor-induced Met dimerization.
Koschut D, Richert L, Pace G, Niemann HH, Mely Y, Orian-Rousseau V., Biochim. Biophys. Acta 1863(7 Pt A), 2016
PMID: 27094128
Statistical analysis of interface similarity in crystals of homologous proteins.
Xu Q, Canutescu AA, Wang G, Shapovalov M, Obradovic Z, Dunbrack RL Jr., J. Mol. Biol. 381(2), 2008
PMID: 18599072
Inference of macromolecular assemblies from crystalline state.
Krissinel E, Henrick K., J. Mol. Biol. 372(3), 2007
PMID: 17681537
Assembly reflects evolution of protein complexes.
Levy ED, Boeri Erba E, Robinson CV, Teichmann SA., Nature 453(7199), 2008
PMID: 18563089
An allosteric mechanism for activation of the kinase domain of epidermal growth factor receptor.
Zhang X, Gureasko J, Shen K, Cole PA, Kuriyan J., Cell 125(6), 2006
PMID: 16777603
High-density miniaturized thermal shift assays as a general strategy for drug discovery.
Pantoliano MW, Petrella EC, Kwasnoski JD, Lobanov VS, Myslik J, Graf E, Carver T, Asel E, Springer BA, Lane P, Salemme FR., J Biomol Screen 6(6), 2001
PMID: 11788061
NIH Image to ImageJ: 25 years of image analysis.
Schneider CA, Rasband WS, Eliceiri KW., Nat. Methods 9(7), 2012
PMID: 22930834


Markieren/ Markierung löschen
Markierte Publikationen

Open Data PUB

Web of Science

Dieser Datensatz im Web of Science®


PMID: 27789707
PubMed | Europe PMC

Suchen in

Google Scholar