Cooperativity

About: Cooperativity is a research topic. Over the lifetime, 7027 publications have been published within this topic receiving 258930 citations. The topic is also known as: cooperativity.

Spontaneous assembly of double-stranded helicates from oligobipyridine ligands and copper(I) cations: structure of an inorganic double helix

Abstract: Two oligobipyridine ligands containing two and three 2,2'-bipyridine subunits separated by 2-oxapropylene bridges have been synthesized and some of their complexation properties with metal ions have been investigated. In particular, with copper(I) they form, respectively, a dinuclear and a trinuclear complex containing two ligand molecules and two or three Cu(I) ions. In view of the pseudotetrahedral coordination geometry of Cu(I) X bis(bipyridine) sites and of NMR data indicating that the present complexes are chiral, one may assign to these dinuclear and trinuclear species a double-helical structure in which two molecular strands are wrapped around two or three Cu(I) ions, which hold them together. These complexes may thus be termed "double-stranded helicates." Determination of the crystal structure of the trinuclear species has confirmed that it is indeed an inorganic double helix, possessing characteristic features (helical parameters, stacking of bipyridine bases) reminiscent of the DNA double helix. This spontaneous formation of an organized structure by oligobipyridine ligands and suitable metal ions opens ways to the design and study of self-assembling systems presenting cooperativity and regulation features. Various further developments may be envisaged along organic, inorganic, and biochemical lines.

Allostery without conformational change. A plausible model.

Abstract: A general model is presented whereby lignand-induced changes in protein dynamics could produce allosteric communication between distinct binding sites, even in the absence of a macromolecular conformational change. Theoretical analysis, based on the statistical thermodynamics of ligand binding, shows that cooperative interaction free energies amounting to several kJ · mol-1 may be generated by this means. The effect arises out of the possible changes in frequencies and amplitudes of macromolecular thermal fluctuations in response to ligand attachment, and can involve all forms of dynamic behaviour, ranging from highly correlated, low-frequency normal mode vibrations to random local anharmonic motions of individual atoms or groups. Dynamic allostery of this form is primarily an entropy effect, and we derive approximate expressions which might allow the magnitude of the interaction in real systems to be calculated directly from experimental observations such as changes in normal mode frequencies and mean-square atomic displacements. Long-range influence of kinetic processes at different sites might also be mediated by a similar mechanism. We suggest that proteins and other biological macromolecules may have evolved to take functional advantage not only of mean conformational states but also of the inevitable thermal fluctuations about the mean.

Escherichia coli single-stranded DNA-binding protein: multiple DNA-binding modes and cooperativities.

Abstract: There are now several well-documented SSBs from both prokaryotes and eukaryotes that function in replication, recombination, and repair; however, no "consensus" view of their interactions with ssDNA has emerged. Although these proteins all bind preferentially and with high affinity to ssDNA, their modes of binding to ssDNA in vitro, including whether they bind with cooperativity, often differ dramatically. This point is most clear upon comparing the properties of the phage T4 gene 32 protein and the E. coli SSB protein. Depending on the solution conditions, Eco SSB can bind ssDNA in several different modes, which display quite different properties, including cooperativity. The wide range of interactions with ssDNA observed for Eco SSB is due principally to its tetrameric structure and the fact that each SSB protomer (subunit) can bind ssDNA. This reflects a major difference between Eco SSB and the T4 gene 32 protein, which binds DNA as a monomer and displays "unlimited" positive cooperativity in its binding to ssDNA. The Eco SSB tetramer can bind ssDNA with at least two different types of nearest-neighbor positive cooperativity ("limited" and "unlimited"), as well as negative cooperativity among the subunits within an individual tetramer. In fact, this latter property, which is dependent upon salt concentration and nucleotide base composition, is a major factor influencing whether ssDNA interacts with all four or only two SSB subunits, which in turn determines the type of intertetramer positive cooperativity. Hence, it is clear that the interactions of Eco SSB with ssDNA are quite different from those of T4 gene 32 protein, and the idea that all SSBs bind to ssDNA as does the T4 gene 32 protein must be amended. Although it is not yet known which of the Eco SSB-binding modes is functionally important in vivo, it is possible that some of the modes are used preferentially in different DNA metabolic processes. In any event, the vastly different properties of the Eco SSB-binding modes must be considered in studies of DNA replication, recombination, and repair in vitro. Since eukaryotic mitochondrial SSBs as well as SSBs encoded by prokaryotic conjugative plasmids are highly similar to Eco SSB, these proteins are likely to show similar complexities. However, based on their heterotrimeric subunit composition, the eukaryotic nuclear SSBs (RP-A proteins) are significantly different from either Eco SSB or T4 gene 32 proteins. Further subclassification of these proteins must await more detailed biochemical and biophysical studies.