The X-ray structures of two mutant crystallin domains shed light on the evolution of multi-domain proteins

Nat Struct Biol. 1996 Mar;3(3):267-74. doi: 10.1038/nsb0396-267.


We use protein engineering and crystallography to simulate aspects of the early evolution of beta gamma-crystallins by observing how a single domain oligomerizes in response to changes in a sequence extension. The crystal structure of the C-terminal domain of gamma beta-crystallin with its four-residue C-terminal extension shows that the domain does not form a symmetric homodimer analogous to the two-domain pairing in beta gamma-crystallins. Instead the C-terminal extension now forms heterologous interactions with other domains leading to the solvent exposure of the natural hydrophobic interface with a consequent loss in protein solubility. However, this domain truncated by just the C-terminal tyrosine forms a symmetric homodimer of domains in the crystal lattice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Biological Evolution*
  • Cattle
  • Crystallins / chemistry*
  • Crystallins / genetics
  • Crystallization
  • Crystallography, X-Ray
  • Macromolecular Substances
  • Models, Molecular
  • Models, Structural
  • Molecular Sequence Data
  • Molecular Weight
  • Peptide Fragments / chemistry
  • Protein Engineering
  • Protein Structure, Secondary*


  • Crystallins
  • Macromolecular Substances
  • Peptide Fragments

Associated data

  • PDB/1DSL
  • PDB/1GAM