Attractive Patchy Protein Interactions: Understanding of protein dimerization

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 in
more or less anisotropic interactions depending on external parameters such as
salt and pH. However, a deeper understanding of these complex
interactions 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 reason
studied the protein lactoferrin. We have found and characterized a
highly directional attraction which combined with Monte Carlo (MC) simulations
show the mechanism as
a 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 strength
both in scattering experiments and
MC simulations, in qualitative agreement.
Further, we show how the directional attraction is effectively behaving as an attractive patch
that 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 calculations
which is related to charge regulation attraction.