Altering dimerization specificity by changes in surface electrostatics.

M J Nohaile; Z S Hendsch; B Tidor; R T Sauer

doi:10.1073/pnas.051624498

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Altering dimerization specificity by changes in surface electrostatics.

M J Nohaile·Z S Hendsch·B Tidor·R T Sauer

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Abstract

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.

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Crystallography, X-Ray Dimerization Genetic Variation Models, Molecular Mutagenesis Nuclear Magnetic Resonance, Biomolecular Protein Structure, Quaternary Protein Structure, Tertiary Repressor Proteins Static Electricity Viral Proteins Viral Regulatory and Accessory Proteins Journal Article Research Support, U.S. Gov't, P.H.S.

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M J Nohaile, Z S Hendsch, B Tidor, R T Sauer. 2001-02-27. Altering dimerization specificity by changes in surface electrostatics.. https://doi.org/10.1073/pnas.051624498

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