Cooperativity in biological systems

Living organisms can sense and respond to external and internal stimuli. Response is demonstrated in many forms including modulation of gene expression profiles, motility, secretion, cell death, etc. Nevertheless, all forms share a basic property: they depend on sensing small changes in the concentration of an effector molecule or subtle conformational changes in a protein and invoking the appropriate molecular response by the relevant signaling pathways. Sensing, transduction, and response to signals may be directly carried out by controlled changes in the conformation or the assembly of pre-existing components(1,2)or may involve changes in gene expression patterns (as in cell differentiation and development), which in turn is carried out by protein-nucleic acid interactions and complex formation. Hence, understanding conformational changes in proteins and nucleic acids, ligand binding, and complex formation play acentral role in advancing our knowledge of cellular dynamics. Large-scale interaction mapping projects continue to provide detailed (though approximate) interaction networks between pairs of proteins (3–6), but fall short of capturing the stability or dynamics of the interactions. Integration of these maps with thermodynamic and kinetic information about conformational changes and binding events in proteins and nucleic acids holds the promise of discovering simple universal mechanisms that explain and relate seemingly disparate biological phenomena at many levels of complexity. In this article, I will explore ‘cooperativity’, one of the most ubiquitous features in molecular biology and discuss how it impacts macromolecular folding, complex assembly, formation of biological networks, and eventually cellular function and pathology.