N-terminal β-strand swapping in a consensus-derived alternative scaffold driven by stabilizing hydrophobic interactions.
The crystal structure of an N-terminal β-strand-swapped consensus-derived tenascin FN3 alternative scaffold has been determined. A comparison with the unswapped structure reveals that the side chain of residue F88 orients differently and packs more tightly with the hydrophobic core of the domain. Dimer formation also results in the burial of a hydrophobic patch on the surface of the domain. Thus, it appears that tighter packing of F88 in the hydrophobic core and burial of surface hydrophobicity provide the driving forces for the N-terminal β-strand swapping, leading to the formation of a stable compact dimer.
Biotechnology Center of Excellence, Janssen Research & Development LLC, Spring House, Pennsylvania, 19477.
Jinquan
J
Luo
Alexey
A
Teplyakov
Galina
G
Obmolova
Thomas J
TJ
Malia
Winnie
W
Chan
Steven A
SA
Jacobs
Karyn T
KT
O'Neil
Gary L
GL
Gilliland
D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D055550:Protein Stability; D017434:Protein Structure, Tertiary; D019063:Tenascin / Q000737:chemistry
D019063:Tenascin
N-terminal β-strand swapping; Tencon; alternative scaffold; domain swapping