Nature Struct. Bio. Vol. 4, 548-552 (1997)
Dalal, S., Balasubramanian, and Regan,
L
Protein Alchemy:
Change b-Sheet into a-Helix
b-sfeet protein
- a) B1 domain of IgG-bindinf protein G
a-Helical protein - b) Rop,
homodimeric four-helix bundle protein
- 63 amino acids - 7
unstructured amino acids = 56 AAs
Transformation - B1 domain to Rop
The hybrid protein - Janus
- after the Roman
god of new beginnings, who bears two faces
- De Novo designed protein
share 50% sequence identity with B1 domain but same structural
fold with Rop.
- 41% identity with
Rop.
Design Strategy
- keep residues with high
a-helix forming propensities
- replace residues with high
b-sheet forming propensities
- hydrophobic residues put in
"a" and "d" positions of a heptad repeat to form the core
- build model - assessed both
visually and by energy minimization calculations
Structural
characterizations