Huntingtin: A Protein with a Peculiar Solvent Accessible Surface

Taking advantage of the last cryogenic electron microscopy structure of human huntingtin, we explored with computational methods its physicochemical properties, focusing on the solvent accessible surface of the protein and highlighting a quite interesting mix of hydrophobic and hydrophilic patterns, with the prevalence of the latter ones. We then evaluated the probability of exposed residues to be in contact with other proteins, discovering that they tend to cluster in specific regions of the protein. We then found that the remaining portions of the protein surface can contain calcium-binding sites that we propose here as putative mediators for the protein to interact with membranes. Our findings are justified in relation to the present knowledge of huntingtin functional annotation.

Automated summary

By utilizing computational methods, the study explored the physicochemical properties of human huntingtin protein based on the last cryogenic electron microscopy structure, highlighting a mix of hydrophobic and hydrophilic patterns on the protein surface. Exposed residues were found to cluster in specific regions, while remaining portions of the surface may contain calcium-binding sites proposed as potential mediators for protein-membrane interactions. These findings are supported by current knowledge of huntingtin functional annotations.