title: The X-ray structures of two mutant crystallin domains shed light on the evolution of multi-domain proteins.
abstract: 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.
authors.affiliation: Department of Crystallography, Birkbeck College, London, UK.
authors.forename: B V
authors.initials: BV
authors.lastname: Norledge
authors.forename: E M
authors.initials: EM
authors.lastname: Mayr
authors.forename: R
authors.initials: R
authors.lastname: Glockshuber
authors.forename: O A
authors.initials: OA
authors.lastname: Bateman
authors.forename: C
authors.initials: C
authors.lastname: Slingsby
authors.forename: R
authors.initials: R
authors.lastname: Jaenicke
authors.forename: H P
authors.initials: HP
authors.lastname: Driessen
mesh_terms: 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
chemical_list: D003459:Crystallins; D046911:Macromolecular Substances; D010446:Peptide Fragments