Cyclic RGD peptides interfere with binding of the Helicobacter pylori protein CagL to integrins αVβ3 and α5β1
| Autor: | Felix Mertink, Jens Conradi, Sylwia Huber, Katharina Gaus, Ulf Strijowski, Steffen Backert, Norbert Sewald, Soledad Royo Gracia |
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| Rok vydání: | 2011 |
| Předmět: |
Clinical Biochemistry
Mutant Integrin Proteomics Peptides Cyclic Biochemistry Protein Structure Secondary Epitope Pilus Structure-Activity Relationship Bacterial Proteins Cell Line Tumor Humans Secretion RGD motif Binding Sites Helicobacter pylori biology Organic Chemistry Integrin alphaVbeta3 biology.organism_classification Molecular biology Protein Structure Tertiary biology.protein Integrin alpha5beta1 |
| Zdroj: | Amino Acids. 43:219-232 |
| ISSN: | 1438-2199 0939-4451 |
| DOI: | 10.1007/s00726-011-1066-0 |
| Popis: | The human pathogen Helicobacter pylori that may cause different gastric diseases exploits integrins for infection of gastric cells. The H. pylori protein CagL present on the outer region of the type IV secretion pilus contains an RGD sequence (-Arg-Gly-Asp-) that enables binding to cells presenting integrins α(5)β(1) and α(V)β(3). This interaction can be inhibited with conformationally designed cyclic RGD peptides derived from the CagL epitope -Ala-Leu-Arg-Gly-Asp-Leu-Ala-. The inhibition of the CagL-α(V)β(3) interaction by different RGD peptides strongly suggests the importance of the RGD motif for CagL binding. CagL point mutants (RAD, RGA) show decreased affinity to integrin α(V)β(3). Furthermore, structure-activity relationship studies with cyclic RGD peptides in a spatial screening approach show the distinct influence of the three-dimensional arrangement of RGD motif on the ability to interfere with this interaction. Resulting from these studies, similar structural requirements for the CagL epitope as previously suggested for other ligands of integrin α(V)β(3) are proposed. |
| Databáze: | OpenAIRE |
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