Structural elements of the osteopontin SVVYGLR motif important for the interaction with alpha(4) integrins

The osteopontin SVVYGLR motif binds the integrins alpha (4)beta (1) and alp ha (9)beta (1). We show that alpha (4)beta (7) also interacts with this mot if and that an SVVYGLR-OH peptide antagonises the alpha (4)beta (7) MAdCAM interaction. The important elements of this motif required to bind alpha (4 )beta (1) and alpha (4)beta (7) were probed using a series of mutated pepti des based around SVVYGLR. Leu167 is important for the interaction with alph a (4) integrins, as is the C-terminal carboxylic acid of Arg168 exposed by thrombin cleavage. The importance of the acidic group means that SVVYGLR ha s structural elements in common with other alpha4 integrin-binding motifs a nd suggests why thrombin cleavage activates this motif. (C) 2001 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemica l Societies.