Cooperativity in biological systems

Document Type: Research Paper


Department of Cell Biology, Harvard Medical School, Boston, MA, USA


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.


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