A STUDY OF STRUCTURAL DETERMINANTS IN THE INTERLEUKIN-1 FOLD

The structures of interleukin-1beta, basic fibroblast growth factor an d Erythrina trypsin inhibitor have been analysed in order to determine whether the hydrophobic core remains conserved, even when the structu res have extremely low sequence similarities. We find that there are s ignificant differences in the way each protein achieves a satisfactory arrangement of core residues and that positions which contribute to t he core of one structure are not guaranteed to contribute to the integ rity of another. Furthermore, the side-chain packing arrangements of t hese core residues vary significantly between the three structures. Du ring this analysis the side-chain rotamers for three independently det ermined interleukin-1beta structures were also compared. It was found that although buried residues are generally in agreement the remaining residues frequently occupy different rotamers in the three structures . This suggests that although meaningful studies are possible for buri ed side-chains the results obtained from equivalent analyses of access ible residues should be treated with caution. These results are discus sed with specific reference to the optimization of side-chain packing in proteins of known structure.