Investigation into the interactions between diadenosine 5',5'''-P1,P4-tetraphosphate and two proteins: molecular chaperone GroEL and cAMP receptor protein

Biochemistry
Julian A TannerAndrew D Miller

Abstract

Diadenosine 5',5'''-P(1),P(4)-tetraphosphate (Ap(4)A) is a dinucleoside polyphosphate found ubiquitously in eukaryotic and prokaryotic cells. Despite Ap(4)A being universal, its functions have proved to be difficult to define, although they appear to have a strong presence during cellular stress. Here we report on our investigations into the nature and properties of putative Ap(4)A interactions with Escherichia coli molecular chaperone GroEL and cAMP receptor protein (CRP). We confirm previous literature observations that GroEL is an Ap(4)A binding protein and go on to prove that binding of Ap(4)A to GroEL involves a set of binding sites (one per monomer) distinct from the well-known GroEL ATP/ADP sites. Binding of Ap(4)A to GroEL appears to enhance ATPase rates at higher temperatures, encourages the release of bound ADP, and may promote substrate protein release through differential destabilization of the substrate protein-GroEL complex. We suggest that such effects should result in enhanced GroEL/GroES chaperoning activities that could be a primary reason for the improved yields of the refolded substrate protein observed during GroEL/GroES-assisted folding and refolding at >or=30 degrees C in the presence of Ap(4)A. In contra...Continue Reading

References

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Citations

Oct 27, 2009·Biochemistry·Alison L SikoraJohn S Blanchard
Apr 22, 2010·The Journal of Biological Chemistry·Birgit RudolphJeannette Winter
Oct 8, 2011·Biochimica Et Biophysica Acta·Hugo Fraga, Rui Fontes
Oct 22, 2011·Bioorganic & Medicinal Chemistry Letters·Wei GuoAndrew D Miller
Dec 13, 2007·Journal of Molecular Recognition : JMR·Rebecca L Rich, David G Myszka
May 24, 2014·Bioorganic & Medicinal Chemistry Letters·M Ameruddin AzharAndrew D Miller
Aug 2, 2016·Future Medicinal Chemistry·Andrew D Miller
Sep 25, 2015·The Journal of Biological Chemistry·Viktor A AnashkinAlexander A Baykov
Dec 8, 2020·Frontiers in Molecular Biosciences·Freya FergusonNikki A Copeland

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