Inter-domain linkers modulate supertertiary structural dynamics in the N-terminal PDZ tandem of PSD-95

Abstract

Multidomain proteins perform a multitude of biological functions facilitated by the diverse interactions of their constituent domains. Often, flexible linker regions connect these domains, allowing them to adopt a series of supertertiary structures. However, it is increasingly evident that linkers act as more than spacers; instead, they can modulate protein-protein interactions as participants at binding interfaces or by effectively limiting the supertertiary conformations. Previously, we showed that the two N-terminal PDZ domains of PSD-95 (PDZ12 tandem), connected by a short and flexible linker, adopt at least two distinct conformations characterized by weak interactions.