Intrinsically unstructured proteins by designelectrostatic interactions can control binding, folding, and function of a helix-loop-helix heterodimer
2013 (English)In: Journal of Peptide Science, ISSN 1075-2617, E-ISSN 1099-1387, Vol. 19, no 8, 461-469 p.Article in journal (Refereed) Published
Intrinsically disordered proteins that exist as unordered monomeric structures in aqueous solution at pH7 but fold into four-helix bundles upon binding to recognized polypeptide targets have been designed. NMR and CD spectra of the monomeric polypeptides show the hallmarks of unordered structures, whereas in the bound state they are highly helical. Analytical ultracentrifugation data shows that the polypeptides bind to their targets to form exclusively heterodimers at neutral pH. To demonstrate the relationship between binding, folding, and function, a catalytic site for ester hydrolysis was introduced into an unordered and largely inactive monomer, but that was structured and catalytically active in the presence of a specific polypeptide target. Electrostatic interactions between surface-exposed residues inhibited the binding and folding of the monomers at pH7. Charge-charge repulsion between ionizable amino acids was thus found to be sufficient to disrupt binding between polypeptide chains despite their inherent propensities for structure formation and may be involved in the folding and function of inherently disordered proteins in biology.
Place, publisher, year, edition, pages
Wiley-Blackwell , 2013. Vol. 19, no 8, 461-469 p.
heterodimer, electrostatic interactions, folding, catalysis
Engineering and Technology
IdentifiersURN: urn:nbn:se:liu:diva-95940DOI: 10.1002/psc.2520ISI: 000321703200001OAI: oai:DiVA.org:liu-95940DiVA: diva2:641766
Funding Agencies|Swedish Research Council||Swedish Foundation for Strategic Research||2013-08-192013-08-122013-08-19