Open AccessAltering dimerization specificity by changes in surface electrostatics
Author(s) -
Michael J. Nohaile,
Zachary S. Hendsch,
Bruce Tidor,
Robert T. Sauer
Publication year - 2001
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.051624498
Subject(s) - electrostatics , protein subunit , static electricity , biophysics , chemistry , protein design , crystallography , peptide sequence , protein structure , biology , biochemistry , physics , gene , quantum mechanics
Arc repressor forms a homodimer in which the subunits intertwine to create a single globular domain. To obtain Arc sequences that fold preferentially as heterodimers, variants with surface patches of excess positive or negative charge were designed. Several but not all oppositely charged sequence pairs showed preferential heterodimer formation. In the most successful design pair, alpha helix B of one subunit contained glutamic acids at positions 43, 46, 47, 48, and 50, whereas the other subunit contained lysines or arginines at these positions. A continuum electrostatic model captures many features of the experimental results and suggests that the most successful designs include elements of both positive and negative design.