Beyond the binding site: the role of the β₂-β₃ loop and extra-domain structures in PDZ domains.

ABSTRACT: A general paradigm to understand protein function is to look at properties of isolated well conserved domains, such as SH3 or PDZ domains. While common features of domain families are well understood, the role of subtle differences among members of these families is less clear. Here, molecular dynamics simulations indicate that the binding mechanism in PSD95-PDZ3 is critically regulated via interactions outside the canonical binding site, involving both the poorly conserved β₂-β₃ loop and an extra-domain helix. Using the CRIPT peptide as a prototypical ligand, our simulations suggest that a network of salt-bridges between the ligand and this loop is necessary for binding. These contacts interconvert between each other on a time scale of a few tens of nanoseconds, making them elusive to X-r

SUBMITTER: Mostarda S 

PROVIDER: S-EPMC3297566 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature