气候变化领域集成服务门户(CCPortal): Ion mobility–mass spectrometry reveals the role of peripheral myelin protein dimers in peripheral neuropathy

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DOI	10.1073/pnas.2015331118
	Ion mobility–mass spectrometry reveals the role of peripheral myelin protein dimers in peripheral neuropathy
	Fantin S.M.; Parson K.F.; Yadav P.; Juliano B.; Li G.C.; Sanders C.R.; Ohi M.D.; Ruotolo B.T.
发表日期	2021
ISSN	00278424
卷号	118 期号:17
英文摘要	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. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Mass spectrometry; Membrane protein; Protein misfolding
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/179738
作者单位	Department of Chemistry, University of Michigan, Ann Arbor, MI 48109, United States; Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, United States; Department of Biochemistry, Vanderbilt University School of Medicine Basic Sciences, Nashville, TN 37240, United States; Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, United States
推荐引用方式 GB/T 7714	Fantin S.M.,Parson K.F.,Yadav P.,等. Ion mobility–mass spectrometry reveals the role of peripheral myelin protein dimers in peripheral neuropathy[J],2021,118(17).
APA	Fantin S.M..,Parson K.F..,Yadav P..,Juliano B..,Li G.C..,...&Ruotolo B.T..(2021).Ion mobility–mass spectrometry reveals the role of peripheral myelin protein dimers in peripheral neuropathy.Proceedings of the National Academy of Sciences of the United States of America,118(17).
MLA	Fantin S.M.,et al."Ion mobility–mass spectrometry reveals the role of peripheral myelin protein dimers in peripheral neuropathy".Proceedings of the National Academy of Sciences of the United States of America 118.17(2021).