Peripheral myelin protein 22 preferentially partitions into ordered phase membrane domains.

Proceedings of the National Academy of Sciences of the United States of America
Justin T MarinkoC R Sanders

Abstract

The ordered environment of cholesterol-rich membrane nanodomains is thought to exclude many transmembrane (TM) proteins. Nevertheless, some multispan helical transmembrane proteins have been proposed to partition into these environments. Here, giant plasma membrane vesicles (GPMVs) were employed to quantitatively show that the helical tetraspan peripheral myelin protein 22 (PMP22) exhibits a pronounced preference for, promotes the formation of, and stabilizes ordered membrane domains. Neither S-palmitoylation of PMP22 nor its putative cholesterol binding motifs are required for this preference. In contrast, Charcot-Marie-Tooth disease-causing mutations that disrupt the stability of PMP22 tertiary structure reduce or eliminate this preference in favor of the disordered phase. These studies demonstrate that the ordered phase preference of PMP22 derives from global structural features associated with the folded form of this protein, providing a glimpse at the structural factors that promote raft partitioning for multispan helical membrane proteins.

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Citations

Sep 16, 2020·Traffic·Yvonne Lange, Theodore L Steck
Aug 8, 2020·Cells·Arne Raasakka, Petri Kursula
Jan 21, 2021·Physical Review. E·Ahis ShresthaChristoph A Haselwandter
Sep 28, 2020·Cellular Signalling·Caglar Gök, William Fuller
Apr 12, 2021·The Journal of Biological Chemistry·Ricardo CaponeAnne K Kenworthy
Mar 13, 2021·Annual Review of Physical Chemistry·Thomas R ShawSarah L Veatch
Apr 25, 2021·Proceedings of the National Academy of Sciences of the United States of America·Sarah M FantinBrandon T Ruotolo
May 3, 2021·The Journal of Biological Chemistry·Justin T MarinkoCharles R Sanders
Feb 2, 2022·The Journal of Physical Chemistry Letters·Itay SchachterMatti Javanainen

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Datasets Mentioned

BETA
GM1

Methods Mentioned

BETA
glycosylation
fluorescence microscopy
transfection
protein folding
Transfections

Software Mentioned

ImageJ
MATLAB
Excel
GraphPad

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