The X-ray structures of two mutant crystallin domains shed light on the evolution of multi-domain proteins.
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.
Norledge
B V
BV
Department of Crystallography, Birkbeck College, London, UK.
Mayr
E M
EM
Glockshuber
R
R
Bateman
O A
OA
Slingsby
C
C
Jaenicke
R
R
Driessen
H P
HP
D000595:Amino Acid Sequence; D000818:Animals; D005075:Biological Evolution; D002417:Cattle; D003459:Crystallins / Q000737:chemistry* / Q000235:genetics; D003460:Crystallization; D018360:Crystallography, X-Ray; D046911:Macromolecular Substances; D008958:Models, Molecular; D008961:Models, Structural; D008969:Molecular Sequence Data; D008970:Molecular Weight; D010446:Peptide Fragments / Q000737:chemistry; D015202:Protein Engineering; D017433:Protein Structure, Secondary
D003459:Crystallins; D046911:Macromolecular Substances; D010446:Peptide Fragments