Cooperativity in biological systems

Abstract

Living organisms can sense and respond to external and internal stimuli. Response isdemonstrated in many forms including modulation of gene expression profiles, motility,secretion, cell death, etc. Nevertheless, all forms share a basic property: they depend on sensingsmall changes in the concentration of an effector molecule or subtle conformational changes ina 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 changesin the conformation or the assembly of pre-existing components(1,2)or may involve changes ingene expression patterns (as in cell differentiation and development), which in turn is carriedout by protein-nucleic acid interactions and complex formation. Hence, understandingconformational changes in proteins and nucleic acids, ligand binding, and complex formationplay acentral role in advancing our knowledge of cellular dynamics. Large-scale interactionmapping projects continue to provide detailed (though approximate) interaction networksbetween pairs of proteins (3–6), but fall short of capturing the stability or dynamics of theinteractions. Integration of these maps with thermodynamic and kinetic information aboutconformational changes and binding events in proteins and nucleic acids holds the promise ofdiscovering simple universal mechanisms that explain and relate seemingly disparate biologicalphenomena at many levels of complexity. In this article, I will explore ‘cooperativity’, one ofthe most ubiquitous features in molecular biology and discuss how it impacts macromolecularfolding, complex assembly, formation of biological networks, and eventually cellular functionand pathology.