A study of structural determinants in the interleukin-1 fold

Area of Science:

• Structural biology
• Protein science
• Biochemistry

Background:

• The hydrophobic core is crucial for protein structure and stability.
• Conserved hydrophobic cores are often assumed across proteins with low sequence similarity.
• Understanding core residue arrangement is key to predicting protein folding and function.

Purpose of the Study:

• To investigate the conservation of hydrophobic cores in proteins with significant sequence dissimilarity.
• To analyze variations in side-chain packing within the hydrophobic cores of different proteins.
• To assess the reliability of side-chain rotamer analysis for buried versus accessible residues.

Main Methods:

• Comparative structural analysis of three proteins: interleukin-1 beta, basic fibroblast growth factor, and Erythrina trypsin inhibitor.
• Examination of hydrophobic core residue arrangement and side-chain packing.
• Comparison of side-chain rotamers across multiple structures of interleukin-1 beta.

Main Results:

• Significant differences were observed in how proteins arrange their core residues.
• Positions contributing to the core in one protein do not necessarily contribute to another's integrity.
• Side-chain packing arrangements within the core vary considerably between the studied structures.
• Buried residues showed agreement across multiple interleukin-1 beta structures, while accessible residues exhibited rotamer variability.

Conclusions:

• Hydrophobic core conservation is not guaranteed in proteins with low sequence similarity.
• Side-chain packing is highly variable, even within the core.
• Analysis of buried side-chain rotamers is more reliable than for accessible residues in structural studies.
• These findings have implications for protein structure prediction and optimization.