Protein activities driven by amino acid composition

A foundational concept in protein biochemistry is that the primary sequence of a protein determines its structure and function. However, some protein regions defy this constraint, with protein activity dictated more by amino acid composition than primary sequence. In this review, we examine the concept of "composition-driven protein activities." We discuss experimental criteria for classifying protein activities as driven by composition, how these criteria relate to primary sequence and composition, and how they have aided in characterizing existing examples of composition-driven activities. This emerging perspective provides a framework for thinking about the relationship between sequence and function in particular types of proteins.