Background: Proteins present a modular organization made up of several domains. Apart
from the domains playing catalytic functions, many others are crucial to recruit interactors. The
latter domains can be defined as "PIDs" (Protein Interaction Domains) and are responsible for pivotal
outcomes in signal transduction and a certain array of normal physiological and disease-related
pathways. Targeting such PIDs with small molecules and peptides able to modulate their interaction
networks, may represent a valuable route to discover novel therapeutics.
Objective: This work represents a continuation of a very recent review describing PIDs able to
recognize post-translationally modified peptide segments. On the contrary, the second part concerns
with PIDs that interact with simple peptide sequences provided with standard amino acids.
Methods: Crucial structural information on different domain subfamilies and their interactomes was
gained by a wide search in different online available databases (including the PDB (Protein Data
Bank), the Pfam (Protein family), and the SMART (Simple Modular Architecture Research Tool)).
Pubmed was also searched to explore the most recent literature related to the topic.
Results and Conclusion: PIDs are multifaceted: they have all diverse structural features and can
recognize several consensus sequences. PIDs can be linked to different diseases onset and progression,
like cancer or viral infections and find applications in the personalized medicine field. Many
efforts have been centered on peptide/peptidomimetic inhibitors of PIDs mediated interactions but
much more work needs to be conducted to improve drug-likeness and interaction affinities of identified