Summary of Study ST002875
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
This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.
| Study ID | ST002875 |
| Study Title | LAT1-4F2hc Lipidomics |
| Study 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-γ (IFN-γ) 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 |
| di.wu2@chem.ox.ac.uk | |
| Phone | +4401865275278 |
| Submit Date | 2023-09-14 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | mzML |
| Analysis Type Detail | LC-MS |
| Release Date | 2024-03-14 |
| Release Version | 1 |
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Collection:
| Collection ID: | CO002981 |
| Collection Summary: | The LAT1-4F2hc complex was buffer-exchanged into 1M ammonium acetate, pH 7.0 with 2 mM OGNG and incubated with 1 µg trypsin overnight at 37 °C. The digested peptide/lipid mixture was dried using a SpeedVac vacuum concentrator (Thermo Fisher Scientific) |
| Sample Type: | HEK cells |
