Summary of project PR001797
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001797. The data can be accessed directly via it's Project DOI: 10.21228/M8F422 This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR001797 |
| Project DOI: | doi: 10.21228/M8F422 |
| Project Title: | LAT1-4F2hc Lipidomics |
| Project Type: | MS identification |
| Project Summary: | The LAT1-4F2hc complex (SLC7A5-SLC3A2) facilitates uptake of essential amino acids, hormones and drugs. Its dysfunction is associated with many cancers and immune/neurological disorders. Here, we apply native mass spectrometry (MS)-based approaches to provide evidence of super-dimer formation (LAT1-4F2hc)2. When combined with lipidomics, and site-directed mutagenesis, we discover four endogenous phosphatidylethanolamine (PE) molecules at the interface and C-terminus of both LAT1 subunits. We find that interfacial PE binding is regulated by 4F2hc-R183 and is critical for regulation of palmitoylation on neighbouring LAT1-C187. Combining native MS with mass photometry (MP) we reveal that super-dimerization is sensitive to pH, and modulated by complex N-glycans on the 4F2hc subunit. Free LAT1 is also present in the lysosome after interferon-? (IFN-?) stimulation suggesting that the assembly of LAT1-4F2hc is regulated by redox dynamics in vivo. Together our results link PTM and lipid binding with regulation and trafficking of the LAT1-4F2hc super dimer. |
| Institute: | University of Oxford |
| Department: | Kavli Institute for Nanoscience Discovery |
| Laboratory: | Prof. Carol Robinson Group |
| Last Name: | Wu |
| First Name: | Di |
| Address: | Kavli Institute for Nanoscience Discovery, University of Oxford, Oxford, OX1 3QU, UK |
| Email: | di.wu2@chem.ox.ac.uk |
| Phone: | +4401865275278 |
Summary of all studies in project PR001797
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST002875 | LAT1-4F2hc Lipidomics | Homo sapiens | University of Oxford | MS* | 2024-03-14 | 1 | 4 | Uploaded data (191.3M)* |
