Computation-guided backbone grafting of a discontinuous motif onto a protein scaffold.
Journal Article (Journal Article)
The manipulation of protein backbone structure to control interaction and function is a challenge for protein engineering. We integrated computational design with experimental selection for grafting the backbone and side chains of a two-segment HIV gp120 epitope, targeted by the cross-neutralizing antibody b12, onto an unrelated scaffold protein. The final scaffolds bound b12 with high specificity and with affinity similar to that of gp120, and crystallographic analysis of a scaffold bound to b12 revealed high structural mimicry of the gp120-b12 complex structure. The method can be generalized to design other functional proteins through backbone grafting.
Full Text
Duke Authors
Cited Authors
- Azoitei, ML; Correia, BE; Ban, Y-EA; Carrico, C; Kalyuzhniy, O; Chen, L; Schroeter, A; Huang, P-S; McLellan, JS; Kwong, PD; Baker, D; Strong, RK; Schief, WR
Published Date
- October 21, 2011
Published In
Volume / Issue
- 334 / 6054
Start / End Page
- 373 - 376
PubMed ID
- 22021856
Electronic International Standard Serial Number (EISSN)
- 1095-9203
Digital Object Identifier (DOI)
- 10.1126/science.1209368
Language
- eng
Conference Location
- United States