A framework for understanding and investigating polyphosphate-protein interactions

Many prokaryotic and eukaryotic cells store inorganic phosphate in the form of polymers called polyphosphate (polyP). There has been an explosion of interest in polyP over the past decade, in part due to newly suggested roles related to diverse aspects of human health. The physical interaction of polyP chains with specific proteins has been proposed to regulate cellular homeostasis and modulate signaling pathways in response to environmental changes. Recently, several studies have challenged existing models for how polyP interacts with its protein targets, while identifying new motifs that are capable of binding to polyP. In this review, we summarize these findings, delineate the functional implications for polyP-protein interactions at the molecular level, and define open questions that should be addressed to propel the field forward.