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

doi:10.1038/s41467-019-09355-y

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

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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, …

Nature communications, Vol.10, 1528

04/04/2019

DOI: https://doi.org/10.1038/s41467-019-09355-y

PMCID: PMC6449406

PMID: 30948714

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Abstract

Multidisciplinary Sciences

Science & Technology

Science & Technology - Other Topics

Cell signalling

Endosomes

Membrane trafficking

Phospholipids

Structural biology

Phox homology (PX) domains are membrane interacting domains that bind to phosphati-dylinositol phospholipids or phosphoinositides, markers of organelle identity in the endocytic system. Although many PX domains bind the canonical endosome-enriched lipid Ptdlns3P, 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 Ptdlns3P, non-specifically to various di- and tri-phosphorylated phosphoinositides, bind both Ptdlns3P 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.

Details

Title: Classification of the human phox homology (PX) domains based on their phosphoinositide binding specificities
Creators: Mintu Chandra - University of Queensland
Yanni K-Y Chin - University of Queensland
Caroline Mas - University of Queensland
J. Ryan Feathers - The University of Texas Southwestern Medical Center
Blessy Paul - University of Queensland
Sanchari Datta - The University of Texas Southwestern Medical Center
Kai-En Chen - University of Queensland
Xinying Jia - University of Queensland
Zhe Yang - University of Queensland
Suzanne J. Norwood - University of Queensland
Biswaranjan Mohanty - Monash University
Andrea Bugarcic - University of Queensland
Rohan D. Teasdale - University of Queensland
W. Mike Henne - The University of Texas Southwestern Medical Center
Mehdi Mobli - University of Queensland
Brett M. Collins - University of Queensland
Publication Details: Nature communications, Vol.10, 1528
Publisher: Springer Nature
Number of pages: 14
Grant note: R35GM119768 / NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) DP160101743 / Australian Research Council (ARC); Australian Research Council APP1136021 / NHMRC Senior Research Fellowship; National Health and Medical Research Council (NHMRC) of Australia APP1099114 / National Health and Medical Research Council; National Health and Medical Research Council (NHMRC) of Australia FT10100925 / ARC Future Fellowship; Australian Research Council
Identifiers: 991013097819902368
Academic Unit: National Centre for Naturopathic Medicine
Language: English
Resource Type: Journal article

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

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