Structural highlights
Publication Abstract from PubMedUltra-tight binding is usually observed for proteins associating with rigidified molecules. Previously, we demonstrated that femtomolar binders derived from the Armadillo repeat proteins (ArmRPs) can be designed to interact very tightly with fully flexible peptides. Here we show for ArmRPs with four and seven sequence-identical internal repeats that the peptide-ArmRP complexes display conformational dynamics. These dynamics stem from transient breakages of individual protein-residue contacts that are unrelated to overall unbinding. The labile contacts involve electrostatic interactions. We speculate that these dynamics allow attaining very high binding affinities, since they reduce entropic losses. Importantly, only NMR techniques can pick up these local events by directly detecting conformational exchange processes without complications from changes in solvent entropy. Furthermore, we demonstrate that the interaction surface of the repeat protein regularizes upon peptide binding to become more compatible with the peptide geometry. These results provide novel design principles for ultra-tight binders. Unexpected dynamics in femtomolar complexes of binding proteins with peptides.,Cucuzza S, Sitnik M, Jurt S, Michel E, Dai W, Muntener T, Ernst P, Haussinger D, Pluckthun A, Zerbe O Nat Commun. 2023 Nov 28;14(1):7823. doi: 10.1038/s41467-023-43596-2. PMID:38016954[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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This page was last modified 11:45, 13 December 2023.