Attractive Patchy Protein Interactions : Understanding of protein dimerization

Abstract: Protein interactions are important in understanding various protein relevant cellular and technological processes.This is a challenging task due to the intrinsically irregular shape and inhomogeneous surface distribution of neutral, charged, hydrophobic amino acid residues. This results inmore or less anisotropic interactions depending on external parameters such assalt and pH. However, a deeper understanding of these complexinteractions is essential in order to understand the behavior of proteins in solution and protein phase diagrams. The aim of this work was to gain a deeper understanding of protein attractions, in particular, anisotropic protein attractions. We have for this reasonstudied the protein lactoferrin. We have found and characterized ahighly directional attraction which combined with Monte Carlo (MC) simulations show the mechanism asa highly directional short-ranged electrostatic attraction, originated from few ionizable amino acids. This gives rise to a non-monotonic dependence of the second virial coefficient, $B_2$, with ionic strengthboth in scattering experiments and MC simulations, in qualitative agreement. Further, we show how the directional attraction is effectively behaving as an attractive patchthat leads to dimerization of lactoferrin under patch attractive conditions.The phase diagram is also determined under patch conditions where new phases are discovered using cryo-transmission electron microscope.Finally, we explored protein capacitance obtained both from titration experiments and MC computer calculationswhich is related to charge regulation attraction.