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