Folding cooperativity and allosteric function in the tandem-repeat protein class.
Philosophical transactions of the Royal Society of London. Series B, Biological sciences
Royal Society Publishing
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Perez-Riba, A., Synakewicz, M., & Itzhaki, L. (2018). Folding cooperativity and allosteric function in the tandem-repeat protein class.. Philosophical transactions of the Royal Society of London. Series B, Biological sciences, 373 (1749)https://doi.org/10.1098/rstb.2017.0188
The term allostery was originally developed to describe structural changes in one binding site induced by the interaction of a partner molecule with a distant binding site , and it has been studied in depth in the field of enzymology [2–5]. Here we discuss the concept of action at a distance in relation to the folding and function of the solenoid class of tandem-repeat proteins such as tetratricopeptide repeats and ankyrin repeats. Distantly located repeats have a fold cooperatively, even though only nearest-neighbour interactions exist in these proteins. A number of repeat-protein scaffolds have been reported to display allosteric effects, transferred through the repeat array, that enable them to direct the activity of the multi-subunit enzymes within which they reside. We also highlight a recently identified group of tandem-repeat proteins, the RRPNN sub-class of tetratricopeptide repeats (TPRs), recent crystal structures of which indicate that they function as allosteric switches to modulate multiple bacterial quorum-sensing mechanisms. We believe that the folding cooperativity of tandem-repeat proteins and the biophysical mechanisms that transform them into allosteric switches are intimately intertwined. This opinion piece aims to combine our understanding of the two areas and develop ideas on their common underlying principles.
Proteins, Allosteric Regulation, Repetitive Sequences, Amino Acid, Protein Folding, Models, Molecular
LSI acknowledges the support of a Senior Fellowship from the UK Medical Research Foundation. AP was supported by a BBSRC Doctoral Training Programme scholarship and an Oliver Gatty Studentship. MS was supported by a BBSRC Doctoral Training Programme scholarship.
External DOI: https://doi.org/10.1098/rstb.2017.0188
This record's URL: https://www.repository.cam.ac.uk/handle/1810/275027