Classification of the human phox homology (PX) domains based on their phosphoinositide binding specificities

• DOI: 10.1038/s41467-019-09355-y
• Publication Date: 2019-04-04T10:04:10Z
• Authors: Mintu Chandra; Yanni K.-Y. Chin; Caroline Mas; J. Ryan Feathers; Blessy Paul; Sanchari Datta; Kai-En Chen; Xinying Jia; Zhe Yang; Suzanne J. Norwood; Biswaranjan Mohanty; Andrea Bugarcic; Rohan D. Teasdale; W. Mike Henne; Mehdi Mobli; Brett M. Collins
• Keywords: Pleckstrin homology domain; Isothermal Titration Calorimetry; Organelle; Homology

Phox homology (PX) domains are membrane interacting that bind to phosphatidylinositol phospholipids or phosphoinositides, markers of organelle identity in the endocytic system. Although many PX canonical endosome-enriched lipid PtdIns3P, others interact with alternative and a precise understanding how these specificities arise has remained elusive. Here we systematically screen all human for their phospholipid preferences using liposome binding assays, biolayer interferometry isothermal titration calorimetry. These analyses define four distinct classes either specifically non-specifically various di- tri-phosphorylated both PtdIns3P other associate none lipids tested. A comprehensive evaluation domain structures reveals two sites explain specificities, providing basis defining predicting functional interactions entire protein family.