The tripeptide RGD is well known for its role in integrin receptor-mediated cell-cell surface adhesion. Here, NMR and transferred NOE studies have been done with the fibrinogen/fibronectin-derived hexapeptide GRGDSP in the presence of sodium dodecyl sulfate (SDS) and purified platelet glycoprotein integrin receptor GPIIb/IIIa. In the presence of SDS and absence of receptor, GRGDSP gives NOE-based distance geometry-generated structures characteristic of two 'nested' β-turns centered at RG and GD. In the presence of integrin GPIIb/IIIa, GRGDSP resonances are chemically shifted and broadened consistent with a dynamic equilibrium between free and receptor 'bound' peptide. NOEs characteristic of the nested β-turns are either absent or weaker indicating a significant conformational change in GRGDSP in the receptor bound state. GRGDSP appears to bind the receptor in a more extended backbone conformation which positions aspartic acid and arginine residues spatially close for potential electrostatic interactions.
|Original language||English (US)|
|Number of pages||8|
|Journal||Biochimica et Biophysica Acta - Protein Structure and Molecular Enzymology|
|State||Published - Aug 15 1996|
Bibliographical noteFunding Information:
F.F. has done this work in partial fulfilment for the Ph.D. requirements at Thomas Jefferson University. This work benefitted from research grants from the W.W. Smith Charitable Trust, Philadelphia, PA, and from the R.W. Johnson Pharmaceutical Research Institute, Springhouse, PA and from use of the high-field NMR facility at the University of Minnesota. We are very grateful to Eric Eccleston and Denisha Walik of the Department of Human Genetics Microchemical Facility, University of Minnesota, for the synthesis of peptides used in this study. The authors also would like to thank Jeff Press for his support for this project.
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