Bacterial Pleckstrin Homology Domains: A Prokaryotic Origin for the PH Domain

Abstract

Pleckstrin homology (PH) domains have been identified only in eukaryotic proteins to date. We have determined crystal structures for three members of an uncharacterized protein family (Pfam PF08000), which provide compelling evidence for the existence of PH-like domains in bacteria (PHb). The first two structures contain a single PHb domain that forms a dome-shaped, oligomeric ring with C5 symmetry. The third structure has an additional helical hairpin attached at the C-terminus and forms a similar but much larger ring with C12 symmetry. Thus, both molecular assemblies exhibit rare, higher-order, cyclic symmetry but preserve a similar arrangement of their PHb domains, which gives rise to a conserved hydrophilic surface at the intersection of the β-strands of adjacent protomers that likely mediates protein–protein interactions. As a result of these structures, additional families of PHb domains were identified, suggesting that PH domains are much more widespread than originally anticipated. Thus, rather than being a eukaryotic innovation, the PH domain superfamily appears to have existed before prokaryotes and eukaryotes diverged.

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Pleckstrin homology-like domain, family A, member 1 (PHLDA1) and cancer

“…PHL domains are evolutionarily conserved and are found in proteins from prokaryotes and eukaryotes (5,6). These domains are composed of 100-120 aa residues, and their properties include binding to phosphatidylinositol lipids (5).…”

Calmodulin and PI(3,4,5)P 3 cooperatively bind to the Itk pleckstrin homology domain to promote efficient calcium signaling and IL-17A production

“…Since its discovery, PH domains have been recognized in proteins from bacteria to mammals (2, 3). Several hundred mammalian proteins that participate in diverse cellular functions contain one or multiple PH domains.…”