Computation-Guided Backbone Grafting of a Discontinuous Motif onto a Protein Scaffold

Journal Article · Tue Feb 07 00:00:00 EST 2012 · Science

DOI:https://doi.org/10.1126/science.1209368· OSTI ID:1033790

Azoitei, Mihai L; Correia, Bruno E; Ban, Yih-En Andrew; Carrico, Chris; Kalyuzhniy, Oleksandr; Chen, Lei; Schroeter, Alexandria; Huang, Po-Ssu; McLellan, Jason S; Kwong, Peter D; Baker, David; Strong, Roland K; Schief, William R ^[1]

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1. UWASH

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.

• Research Organization: Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
• Sponsoring Organization: FOREIGNOTHER
• OSTI ID: 1033790
• Journal Information: Science, Vol. 334, Issue 6054; ISSN 0193-4511
• Country of Publication: United States
• Language: ENGLISH

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
60 APPLIED LIFE SCIENCES
AFFINITY
AIDS VIRUS
DESIGN
FUNCTIONALS
PROTEIN ENGINEERING
PROTEINS
SPECIFICITY