Molecular shape and prominent role of beta-strand swapping in organization of dUTPase oligomers.
Most dUTP pyrophosphatases (dUTPases) are homotrimers with interfaces formed between subunit surfaces, in the central channel, and by C-terminal beta-strand swapping. Analysis of intersubunit interactions reveals an important cohesive role for the C-terminus. This is reflected in the crystal structure of fruitfly dUTPase displaying a dimeric organization in crystals grown in alcohol solution, where only beta-strand swapping interactions between subunits are retained from the usual trimer structure. Mutations of a suggested hinge proline destabilize human and Escherichia coli dUTPases without preventing trimeric organization. Trimer formation was, however, prevented in the human enzyme by truncating the C-terminus before the swapping arm. The molecular shape of full-length enzymes in solution reveals the localization and variation in flexibility of N- and C-terminal segments.
Takács
Eniko
E
Institute of Enzimology, BRC, Hungarian Academy of Sciences, Budapest, Hungary.
Barabás
Orsolya
O
Petoukhov
Maxim V
MV
Svergun
Dmitri I
DI
Vértessy
Beáta G
BG
D000595:Amino Acid Sequence; D000818:Animals; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D004789:Enzyme Activation; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011755:Pyrophosphatases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment
D011755:Pyrophosphatases; C020020:dUTP pyrophosphatase