Structural requirements of XXXX -containing disintegrins for functional interaction with alpha 4 beta 1 and alpha 9 beta1 integrins.

@entity1 @entity535 @entity19 @entity8431 @entity71028
Three non-RGD-containing disintegrins, VLO5, EO5, and EC3, belong to the heterodimeric family of these snake venom-derived proteins. They are potent inhibitors of certain leukocyte integrins such as alpha4beta1, alpha4beta7, and alpha9beta1, and act through the @entity8431 motif present in one of their subunits. However, the selectivity of these disintegrins to interact with integrins is related to the @entity535 composition of the integrin-binding loop in the @entity8431 -containing subunit. The most important @entity535 is that preceding the @entity8431 motif. In vitro experiments in adhesion and ELISA assays revealed that the @entity71028 -containing disintegrins, VLO5 and EO5, appeared to be very potent inhibitors of @entity1 alpha4beta1 and alpha9beta1 and less effective in inhibition of the alpha4beta7 integrin. The reverse effect was observed for the AMLD-containing disintegrin, EC3. The data with native disintegrins were confirmed by experiments with synthetic peptides displaying @entity71028 and AMLD motifs. The @entity8431 -containing disintegrins showed differential activities to inhibit @entity1 and @entity19 alpha4beta1 integrin. EC3 was a weaker inhibitor of @entity1 integrin, whereas VLO5 and EO5 less actively inhibited @entity19 alpha4beta1. These data describe a useful set of potent and selective integrin antagonists and suggest conformational requirements of @entity1 and @entity19 integrins for interaction with ligands.
