Interaction of the α2A domain of integrin with small collagen fragments.
10.1007/s13238-010-0038-6
- Author:
Hans-Christian SIEBERT
1
;
Monika BURG-RODERFELD
2
;
Thomas ECKERT
2
;
Sabine STÖTZEL
2
;
Ulrike KIRCH
2
;
Tammo DIERCKS
3
;
Martin J HUMPHRIES
4
;
Martin FRANK
5
;
Rainer WECHSELBERGER
6
;
Emad TAJKHORSHID
7
;
Steffen OESSER
8
Author Information
1. Institut für Biochemie und Endokrinologie, Veterinärmedizinische Fakultät, Justus-Liebig-Universität Gießen, Frankfurter Str. 100, 35392, Gießen, Germany. Hans-Christian.Siebert@vetmed.uni-giessen.de.
2. Institut für Biochemie und Endokrinologie, Veterinärmedizinische Fakultät, Justus-Liebig-Universität Gießen, Frankfurter Str. 100, 35392, Gießen, Germany.
3. CiC bioGUNE, Parque Tecnológico de Bizkaia, Edificio 800, 48160, Derio, Spain.
4. Wellcome Trust Centre for Cell-Matrix Research, School of Biological Sciences, University of Manchester, 2.205 Stopford Building, Oxford Road, Manchester, M13 9PT, UK.
5. Molecular Structure Analysis Core Facility, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, 69120, Heidelberg, Germany.
6. Utrecht Facility for High-resolution NMR, Bijvoetcenter for Biomolecular Research Utrecht University, Padualaan 8, 3584CH, Utrecht, The Netherlands.
7. Department of Biochemistry, Beckman Institute, and Center for Biophysics and Computational Biology, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
8. Collagen Research Institute, Schauenburgerstr. 116, D-24118, Kiel, Germany.
- Publication Type:Journal Article
- MeSH:
Animals;
Collagen;
chemistry;
metabolism;
Humans;
Integrins;
metabolism;
Magnetic Resonance Spectroscopy;
Molecular Dynamics Simulation;
Peptides;
chemistry;
metabolism;
Protein Binding;
Protein Structure, Tertiary;
Signal Transduction
- From:
Protein & Cell
2010;1(4):393-405
- CountryChina
- Language:English
-
Abstract:
We here present a detailed study of the ligand-receptor interactions between single and triple-helical strands of collagen and the α2A domain of integrin (α2A), providing valuable new insights into the mechanisms and dynamics of collagen-integrin binding at a sub-molecular level. The occurrence of single and triple-helical strands of the collagen fragments was scrutinized with atom force microscopy (AFM) techniques. Strong interactions of the triple-stranded fragments comparable to those of collagen can only be detected for the 42mer triple-helical collagen-like peptide under study (which contains 42 amino acid residues per strand) by solid phase assays as well as by surface plasmon resonance (SPR) measurements. However, changes in NMR signals during titration and characteristic saturation transfer difference (STD) NMR signals are also detectable when α2A is added to a solution of the 21mer single-stranded collagen fragment. Molecular dynamics (MD) simulations employing different sets of force field parameters were applied to study the interaction between triple-helical or single-stranded collagen fragments with α2A. It is remarkable that even single-stranded collagen fragments can form various complexes with α2A showing significant differences in the complex stability with identical ligands. The results of MD simulations are in agreement with the signal alterations in our NMR experiments, which are indicative of the formation of weak complexes between single-stranded collagen and α2A in solution. These results provide useful information concerning possible interactions of α2A with small collagen fragments that are of relevance to the design of novel therapeutic A-domain inhibitors.
