ArticleProceedings of the National Academy of Sciences of the United States of America2021
Ion mobility-mass spectrometry reveals the role of peripheral myelin protein dimers in peripheral neuropathy.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 31 citations in OpenAlex.
- Peripheral Myelin Protein-22 and Its Prominence in Charcot-Marie-Tooth Disease.Chemical reviews · 2026Review
- Charcot-Marie-Tooth disease type 1E: clinical natural history and molecular impact of PMP22 variants.Brain : a journal of neurology · 2026Article
- Native Top-Down Analysis of Membrane Protein Complexes Directly From In Vitro and Native Membranes.Molecular & cellular proteomics : MCP · 2025Article
- Charcot-Marie-Tooth disease type 1E: Clinical Natural History and Molecular Impact ofmedRxiv : the preprint server for health sciences · 2025Article
- Native Proteomics by Capillary Zone Electrophoresis-Mass Spectrometry.Angewandte Chemie (International ed. in English) · 2024Article
- Disrupting the transmembrane domain interface between PMP22 and MPZ causes peripheral neuropathy.iScience · 2024Article
- Native mass spectrometry of proteoliposomes containing integral and peripheral membrane proteins.Chemical science · 2023Article
- Development of an Automated, High-Throughput Methodology for Native Mass Spectrometry and Collision-Induced Unfolding.Analytical chemistry · 2023Article
- Collision Induced Unfolding Enables the Quantitation of Isomass Biotherapeutics in Complex Biological Matrices.Journal of the American Society for Mass Spectrometry · 2023Article
- Studying Membrane Protein-Lipid Specificity through Direct Native Mass Spectrometric Analysis from Tunable Proteoliposomes.Journal of the American Society for Mass Spectrometry · 2023Article
- Infrared Photoactivation Enables Improved Native Top-Down Mass Spectrometry of Transmembrane Proteins.Analytical chemistry · 2023Article
- Direct determination of oligomeric organization of integral membrane proteins and lipids from intact customizable bilayer.Nature methods · 2023Article
- Mass spectrometry of intact membrane proteins: shifting towards a more native-like context.Essays in biochemistry · 2023Review
- Article
- Mass Spectrometry Methods for Measuring Protein Stability.Chemical reviews · 2022Review
- Collision Cross Sections for Native Proteomics: Challenges and Opportunities.Journal of proteome research · 2022Article
- Charge Engineering Reveals the Roles of Ionizable Side Chains in Electrospray Ionization Mass Spectrometry.JACS Au · 2021Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Peripheral myelin protein (PMP22) is an integral membrane protein that traffics inefficiently even in wild-type (WT) form, with only 20% of the WT protein reaching its final plasma membrane destination in myelinating Schwann cells. Misfolding of PMP22 has been identified as a key factor in multiple peripheral neuropathies, including Charcot-Marie-Tooth disease and Dejerine-Sottas syndrome. While biophysical analyses of disease-associated PMP22 mutants show altered protein stabilities, leading to reduced surface trafficking and loss of PMP22 function, it remains unclear how destabilization of PMP22 mutations causes mistrafficking. Here, native ion mobility-mass spectrometry (IM-MS) is used to compare the gas phase stabilities and abundances for an array of mutant PM22 complexes. We find key differences in the PMP22 mutant stabilities and propensities to form homodimeric complexes. Of particular note, we observe that severely destabilized forms of PMP22 exhibit a higher propensity to dimerize than WT PMP22. Furthermore, we employ lipid raft-mimicking SCOR bicelles to study PMP22 mutants, and find that the differences in dimer abundances are amplified in this medium when compared to micelle-based data, with disease mutants exhibiting up to 4 times more dimer than WT when liberated from SCOR bicelles. We combine our findings with previous cellular data to propose that the formation of PMP22 dimers from destabilized monomers is a key element of PMP22 mistrafficking.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.