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Published December 2007 | Published + Supplemental Material
Journal Article Open

A de novo designed protein-protein interface


As an approach to both explore the physical/chemical parameters that drive molecular self-assembly and to generate novel protein oligomers, we have developed a procedure to generate protein dimers from monomeric proteins using computational protein docking and amino acid sequence design. A fast Fourier transform-based docking algorithm was used to generate a model for a dimeric version of the 56-amino-acid β1 domain of streptococcal protein G. Computational amino acid sequence design of 24 residues at the dimer interface resulted in a heterodimer comprised of 12-fold and eightfold variants of the wild-type protein. The designed proteins were expressed, purified, and characterized using analytical ultracentrifugation and heteronuclear NMR techniques. Although the measured dissociation constant was modest (~300 µM), 2D-[^1H,^(15)N]-HSQC NMR spectra of one of the designed proteins in the absence and presence of its binding partner showed clear evidence of specific dimer formation.

Additional Information

© 2007 The Protein Society. Published by Cold Spring Harbor Laboratory Press. Received July 16, 2007; Final Revision September 21, 2007; Accepted September 21, 2007. This work was supported by the Howard Hughes Medical Institute, the Ralph M. Parsons Foundation, DARPA, the Institute for Collaborative Biotechnologies through grant DAAD19-03-D-0004 from the U.S. Army Research Office, and an IBM Shared University Research Grant.

Attached Files

Published - Huang_2007_Protein_Sci._A_de_novo_designed_protein-protein.pdf

Supplemental Material - Huang_Supp.pdf


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