Protein Surface Interactions—Theoretical and Experimental Studies

Abstract

In this review, we briefly describe a theoretical discussion of protein folding, presenting the relative contribution of the hydrophobic effect versus the stabilization of proteins via direct surface forces that sometimes may be overlooked. We present NMR-based studies showing the stability of proteins lacking a hydrophobic core which in turn present hydrophobic surface clusters, such as plant defensins. Protein dynamics measurements by NMR are the key feature to understand these dynamic surface clusters. We contextualize the measurement of protein dynamics by nuclear relaxation and the information available at protein surfaces and water cavities. We also discuss the presence of hydrophobic surface clusters in multidomain proteins and their participation in transient interactions which may regulate the function of these proteins. In the end, we discuss how surface interaction regulates the reactivity of certain protein post-translational modifications, such as S-nitrosation.

Structure-Function Relationship of the Disintegrin Family: Sequence Signature and Integrin Interaction

“…It was recently proposed that these proteins are stabilized by hydrophobic surface clusters acting as an independent folding unit. In the absence of a canonical hydrophobic core, the surface clusters promote the folding by the interaction of exposed hydrophobic residues with the adjacent side chains regulated by solvation forces ( Almeida et al, 2021 ).…”

Physical-Chemical Features Selection Reveals That Differences in Dipeptide Compositions Correlate Most with Protein-Protein Interactions

“…Third, the presence of charged amino acids in dipeptides can lead to electrostatic interactions that modulate PPI, especially between positively- and negatively-charged amino acids [53]. Fourth, differences in hydrophobicity within dipeptides can also influence interactions, particularly hydrophobic interactions [35].…”

“…Dipeptides with specific combinations of charged amino acids may create favorable or unfavorable electrostatic environments for PPI. Finally, some dipeptide compositions may contain hydrophobic amino acids, which tend to cluster together in the protein’s core [3, 51], while others may have hydrophilic amino acids exposed on the protein’s surface [1, 46]. Differences in dipeptide compositions can lead to variations in hydrophobic and hydrophilic regions, influencing protein-protein interactions, especially those that involve hydrophobic interactions, and dipeptide composition can be targeted to affect protein-protein interactions [26].…”

Chameleon Sequences: Ordered or Disordered

“…IDRs sequences have often low hydropathy, i.e. hydrophilic sequences, so these sequences do not have the conditions to fold 27 . Therefore, it is expected that more chameleon sequences will be located in the inner parts of the protein.…”