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

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

Research output: Contribution to journalArticleResearchpeer-review

15 Citations (Scopus)

Abstract

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

Original languageEnglish
Article number1528
Number of pages14
JournalNature Communications
Volume10
Issue number1
DOIs
Publication statusPublished - 4 Apr 2019

Cite this

Chandra, M., Chin, Y. K. Y., Mas, C., Feathers, J. R., Paul, B., Datta, S., Chen, K. E., Jia, X., Yang, Z., Norwood, S. J., Mohanty, B., Bugarcic, A., Teasdale, R. D., Henne, W. M., Mobli, M., & Collins, B. M. (2019). Classification of the human phox homology (PX) domains based on their phosphoinositide binding specificities. Nature Communications, 10(1), [1528]. https://doi.org/10.1038/s41467-019-09355-y