Fakultät für Chemie - Former
Uni von A-Z
Bielefeld University > Department of Chemistry > Organic Chemistry III > Team > Former

Personal data for Dr. Jens Conradi

  Dr. Jens Conradi
Dr. Jens Conradi
PhD student
Room: F2-219
Phone: 0521 106 2151

Binding of the Helicobacter pylori protein CagL to integrins is inhibited by cyclic RGD peptides

The gram-negative bacterium Helicobacter pylori (Hp) is a type1-carcinogen, that exploits human gastric epithelial cells in a highly specific way. Today about 50% of the world population carries Hp, and this infection may induce gastric diseases from chronic gastritis to cancer [1].

CagL is a key protein in the entry mechanism of Hp, exploiting gastric epithelial cells. For the injection into gastric epithelial cells, Hp uses a type IV secretion system (T4SS). The T4SS machinery is a multi-protein complex, spanning the inner and outer membrane of Hp and building extracellular pili. With the T4SS Hp is able to secrete substrates (CagA, peptidoglycan). It is assumed that CagL is bound in the tip of the T4SS pilus and is therefore most probably responsible for triggering the interaction between the T4SS pilus and α5β1 integrins of the gastric epithelial cells. After integrin clustering the CagA protein and peptidoglycans are injected, effecting numerous cellular events like nuclear signaling, disruption of cell-to-cell junctions and membrane dynamics [2]. Therefore, it is of great interest to understand the integrin-binding capacity of CagL and to uncover its binding motif. The tripeptide sequence RGD has been shown to be a main recognition sequence in the binding motif.

Recombinant CagL was overexpressed in E. coli and purified using a His6-Tag. Binding of CagL to different integrins was investigated using cell adhesion assays and surface plasmon resonance. Different cyclic RGD penta- and hexapeptides were synthesized that might mimic the native CagL RGD recognition sequence with its adjacent amino acids. A competitive cell adhesion assay was established to elucidate IC50 values of different cyclic RGD peptides, using cell lines mainly expressing α5β1 integrins and αVβ3 integrins, respectively. In combination with conformational analysis by NMR and MD calculations it was possible to obtain a better insight for the inhibition of the CagL binding to integrins [3]. With recombinant CagL point mutants, it is possible to examine the binding compatibilities of CagL to integrins even better.


[1] A.R. Sepulveda, D.Y. Graham, Gastroenterol. Clin. North. Am. 31: 517-535, 2002.

[2] T. Kwok, D. Zabler, S. Urman, M. Rohde, R. Hartig, S. Wessler, R. Misselwitz, J. Berger, N. Sewald, W. König, S. Backert, Nature 449: 862-6, 2007.

[3] S. Urman, K. Gaus, Y. Yang, U. Strijowski, N. Sewald, S. De Pol, O. Reiser, Angew. Chem. 119: 4050-4053, 2007; Angew. Chem. Int. Ed. 46: 3976-3978, 2007.