The Charge Distribution on a Protein Surface Determines Whether Productive or Futile Encounter Complexes Are Formed

Biochemistry, vol. 60, pp. 747–755

Abstract

High Resolution Image Download MS PowerPoint Slide Protein complex formation depends strongly on electrostatic interactions. The distribution of charges on the surface of redox proteins is often optimized by evolution to guide recognition and binding. To test the degree to which the electrostatic interactions between cytochrome c peroxidase (CcP) and cytochrome c (Cc) are optimized, we produced five CcP variants, each with a different charge distribution on the surface. Monte Carlo simulations show that the addition of negative charges attracts Cc to the new patches, and the neutralization of the charges in the regular, stereospecific binding site for Cc abolishes the electrostatic interactions in that region entirely. For CcP variants with the charges in the regular binding site intact, additional negative patches slightly enhance productive complex formation, despite disrupting the optimized charge distribution. Removal of the charges in the regular binding site results in a dramatic decrease in the complex formation rate, even in the presence of highly negative patches elsewhere on the surface. We conclude that additional charge patches can result in either productive or futile encounter complexes, depending on whether negative residues are located also in the regular binding site.

Authors 4

1. Antonella Di Savino Aachen Institute of Chemistry

   Leiden University

   Affiliation as printed

   Leiden University, Institute of Chemistry, Einsteinweg 55, 2333 CC Leiden, The Netherlands

2. Johannes M. Foerster

   University of Bayreuth

   Affiliation as printed

   University of Bayreuth, Computational Biochemistry, Universitätsstraße 30, NW I, 95447 Bayreuth, Germany

3. G. Matthias Ullmann

   University of Bayreuth

   Affiliation as printed

   University of Bayreuth, Computational Biochemistry, Universitätsstraße 30, NW I, 95447 Bayreuth, Germany

4. Marcellus Ubbink corresponding Aachen Institute of Chemistry

   Leiden University

   Affiliation as printed

   Leiden University, Institute of Chemistry, Einsteinweg 55, 2333 CC Leiden, The Netherlands