Protein & Cell

, Volume 1, Issue 4, pp 393–405 | Cite as

Interaction of the α2A domain of integrin with small collagen fragments

  • Hans-Christian Siebert
  • Monika Burg-Roderfeld
  • Thomas Eckert
  • Sabine Stötzel
  • Ulrike Kirch
  • Tammo Diercks
  • Martin J. Humphries
  • Martin Frank
  • Rainer Wechselberger
  • Emad Tajkhorshid
  • Steffen Oesser
Research Article


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.


integrin-collagen interaction NMR SPR AFM molecular modeling 

Supplementary material

13238_2010_38_MOESM1_ESM.pdf (603 kb)
Supplementary material, approximately 603 KB.


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Copyright information

© Higher Education Press and Springer-Verlag Berlin Heidelberg 2010

Authors and Affiliations

  • Hans-Christian Siebert
    • 1
  • Monika Burg-Roderfeld
    • 1
  • Thomas Eckert
    • 1
  • Sabine Stötzel
    • 1
  • Ulrike Kirch
    • 1
  • Tammo Diercks
    • 2
    • 3
  • Martin J. Humphries
    • 4
  • Martin Frank
    • 5
  • Rainer Wechselberger
    • 3
  • Emad Tajkhorshid
    • 6
  • Steffen Oesser
    • 7
  1. 1.Institut für Biochemie und Endokrinologie, Veterinärmedizinische FakultätJustus-Liebig-Universität GießenGießenGermany
  2. 2.CiC bioGUNEDerioSpain
  3. 3.Utrecht Facility for High-resolution NMRBijvoetcenter for Biomolecular Research Utrecht UniversityUtrechtThe Netherlands
  4. 4.Wellcome Trust Centre for Cell-Matrix Research, School of Biological SciencesUniversity of ManchesterManchesterUK
  5. 5.Molecular Structure Analysis Core FacilityDeutsches KrebsforschungszentrumHeidelbergGermany
  6. 6.Department of Biochemistry, Beckman Institute, and Center for Biophysics and Computational BiologyUniversity of Illinois at Urbana-ChampaignUrbanaUSA
  7. 7.Collagen Research InstituteKielGermany

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