Charge Interactions in a Highly Charge-Depleted Protein

Stefan Hervø-Hansen, Casper Højgaard, Kristoffer Enøe Johansson, Yong Wang, Khadija Wahni, David Young, Joris Messens, Kaare Teilum, Kresten Lindorff-Larsen, Jakob Rahr Winther

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskriftPeer review

1 Citering (SciVal)

Sammanfattning

Electrostatic forces are important for protein folding and are favored targets of protein engineering. However, interactions between charged residues are difficult to study because of the complex network of interactions found in most proteins. We have designed a purposely simple system to investigate this problem by systematically introducing individual and pairs of charged and titratable residues in a protein otherwise free of such residues. We used constant pH molecular dynamics simulations, NMR spectroscopy, and thermodynamic double mutant cycles to probe the structure and energetics of the interaction between the charged residues. We found that the partial burial of surface charges contributes to a shift in pKa value, causing an aspartate to titrate in the neutral pH range. Additionally, the interaction between pairs of residues was found to be highly context dependent, with some pairs having no apparent preferential interaction, while other pairs would engage in coupled titration forming a highly stabilized salt bridge. We find good agreement between experiments and simulations and use the simulations to rationalize our observations and to provide a detailed mechanistic understanding of the electrostatic interactions.

Originalspråkengelska
Sidor (från-till)2500–2508
TidskriftJournal of the American Chemical Society
Volym143
Utgåva6
DOI
StatusPublished - 2021

Ämnesklassifikation (UKÄ)

  • Biofysik

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