Supertertiary protein structure affects an allosteric network

Significance Protein function can be allosterically regulated by changes in structure or dynamics. PDZ domains are classic examples for studies of allostery in single protein domains. However, PDZ domains are often found in multidomain proteins; in particular, PDZ3 is located in a supramodule containing three domains. The allosteric network in PDZ3 has never been studied in the presence of the adjacent domains. Here we map the allosteric network for a PDZ3:ligand complex, both in isolation and in the context of a supramodule. We demonstrate that the allosteric network is highly dependent on this supertertiary structure, with broad implications for studies of allostery in single domains.