A Dominant Factor for Structural Classification of Protein Crystals

Area of Science:

• Structural biology
• Biophysics
• Computational biology

Background:

• An increasing number of solved protein crystal structures provide valuable data on protein shape and atom geometry.
• Understanding the structural diversity within a single protein type is of significant interest.

Purpose of the Study:

• To broadly examine the hypothesis that multiple crystal structures of a single protein can be classified into distinct groups based on structural similarity.
• To identify the primary factors contributing to observed structural variations in proteins.

Main Methods:

• Cluster analysis was applied to crystal structures of five proteins: hemoglobin (Hb), myoglobin (Mb), human serum albumin (HSA), hen egg-white lysozyme (HEWL), and human immunodeficiency virus type 1 protease (HIV-1 PR).
• Data was downloaded from the Protein Data Bank (PDB).

Main Results:

• Cluster analysis separated Hb (n=146) into five groups, Mb (n=284) into six, HEWL (n=336) into five, HSA (n=63) into three, and HIV-1 PR (n=488) into six groups.
• The primary factors influencing structural separation were identified as the crystal space group and crystallizing agents.
• Amino acid mutation was found to be a minor factor, with species of protein origin being significant for Hb and Mb classification.

Conclusions:

• Protein crystal structures exhibit significant diversity that can be systematically classified using cluster analysis.
• Crystal packing (space group) and crystallization conditions are major determinants of protein structure in crystals.
• Species of origin significantly impacts structural classification when amino acid sequence differences are substantial.