NOE-DERIVED CONFORMATION OF GRGDSP CELL-ADHESION RECOGNITION SITE IN THE PRESENCE OF SDS MICELLES AND INTEGRIN RECEPTOR GPIIB IIIA/

The tripeptide RGD is well known for its role in integrin receptor-med iated cell-cell surface adhesion. Here, NMR and transferred NOE studie s have been done with the fibrinogen/fibronectin-derived hexapeptide G RGDSP in the presence of sodium dodecyl sulfate (SDS) and purified pla telet glycoprotein integrin receptor GPIIb/IIIa. In the presence of SD S and absence of receptor, GRGDSP gives NOE-based distance geometry-ge nerated structures characteristic of two 'nested' beta-turns centered at RG and GD. In the presence of integrin GPIIb/IIIa, GRGDSP resonance s are chemically shifted and broadened consistent with a dynamic equil ibrium between free and receptor 'bound' peptide. NOEs characteristic of the nested beta-turns are either absent or weaker indicating a sign ificant conformational change in GRGDSP in the receptor bound state. G RGDSP appears to bind the receptor in a more extended backbone conform ation which positions aspartic acid and arginine residues spatially cl ose for potential electrostatic interactions.