Protein function machinery: from basic structural units to modulation of activity

•Closed loops are universal basic units of globular proteins.•Enzymatic functions are combined from elementary functional loops.•Structural dynamics is the cornerstone of the protein function and its regulation.•Intrinsic disorder, intermolecular interactions, and allostery work in modulation of protein activity.•Post-translational modification is an intricate mechanism of the regulation of protein function.

Contemporary protein structure is a result of the trade off between the laws of physics and the evolutionary selection. The polymer nature of proteins played a decisive role in establishing the basic structural and functional units of soluble proteins. We discuss how these elementary building blocks work in the hierarchy of protein domain structure, co-translational folding, as well as in enzymatic activity and molecular interactions. Next, we consider modulators of the protein function, such as intermolecular interactions, disorder-to-order transitions, and allosteric signaling, acting via interference with the protein's structural dynamics. We also discuss the post-translational modifications, which is a complementary intricate mechanism evolved for regulation of protein functions and interactions. In conclusion, we assess an anticipated contribution of discussed topics to the future advancements in the field.