Chromosome and protein folding: In search for unified principles

Structural biology has traditionally focused on the structures of proteins, short nucleic acids, small molecules, and their complexes. However, it is now widely recognized that the 3D organization of chromosomes should also be included in this list, despite significant differences in scale and complexity of organization. Here we highlight some notable similarities between the folding processes that shape proteins and chromosomes. Both biomolecules are folded by two types of processes: the affinity-mediated interactions, and by active (ATP-dependent) processes. Both chromosome and proteins in vivo can have partially unstructured and non-equilibrium ensembles with yet to be understood functional roles. By analyzing these biological systems in parallel, we can uncover universal principles of biomolecular organization that transcend specific biopolymers. •Interphase chromosomes are not nearly as structured as folded proteins, yet chromosomes are not unstructured either.•Proteins and chromosomes are folded by affinities between their elements and by active processes.•Active processes of folding are loop extrusion in chromosomes, and co-translational and chaperon-mediated in proteins.•Active processes not only facilitate folding but also generate folding patterns by placing pause site along the sequence.•Functional roles of these activity-driven and not fully structured organizations of both biopolymers are yet to be understood.