Structure–function relationships in protein homorepeats

Abstract

Homorepeats (or polyX), protein segments containing repetitions of the same amino acid, are abundant in proteomes from all kingdoms of life and are involved in crucial biological functions as well as several neurodegenerative and developmental diseases. Mainly inserted in disordered segments of proteins, the structure/function relationships of homorepeats remain largely unexplored. In this review, we summarize present knowledge for the most abundant homorepeats, highlighting the role of the inherent structure and the conformational influence exerted by their flanking regions. Recent experimental and computational methods enable residue-specific investigations of these regions and promise novel structural and dynamic information for this elusive group of proteins. This information should increase our knowledge about the structural bases of phenomena such as liquid–liquid phase separation and trinucleotide repeat disorders.