The physical underpinnings of the property of allostery in proteins remains an area of active study. In particular, there is interest in learning the extent to which allostery differs among related proteins. The family of Protein Tyrosine Phosphatases (PTPs) is one such example, with involvement in processes ranging from leptin and insulin signaling to carcinogenesis. This functional diversity may be attributed to more than differences in aspects such as expression across cell types and subcellular localization, and instead may involve allosteric rewiring within a similar structural architecture. Prior work has investigated the allosteric network of the founding member, Protein Tyrosine Phosphatase 1B (PTP1B). However, the Protein Data Bank (PDB) houses over 600 crystal structures spanning over fifty distinct PTPs, representing everything from apo to bound and wild type to mutant structures. This trove of structures represents an opportunity to better understand how allostery differs between PTPs. We are developing an approach based on identifying networks of dynamic residues that interact via conformational changes. Our pipeline called MultiRIN (Multiple Residue Interaction Networks) uses crystallographic alternate conformations and any changes thereof to extract such networks. Extending this network analysis across all PTPs allows us insights into the global allosteric network in this family, and allows us to dissect aspects that are conserved versus unique among PTPs. This information is crucial not only for understanding the molecular basis of the non-overlapping regulatory roles, but also for identifying unique allosteric target sites across different PTPs.
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