Effects of palmitoylation on membrane protein partitioning into lipid domains in model cellular membranes
Shishi Wu(吴施施)1,2 and Qing Liang(梁清)1,2,†
1 Department of Physics, Zhejiang Normal University, Jinhua 321004, China; 2 Zhejiang Institute of Photoelectronics & Zhejiang Institute for Advanced Light Source, Zhejiang Normal University, Jinhua 321004, China
Abstract The partitioning of membrane proteins into lipid domains in cellular membranes is closely associated with the realization of the protein functions and it is influenced by various factors such as the post-translational modification of palmitoylation. However, the molecular mechanism of the effect of palmitoylation on membrane protein partitioning into the lipid domains remains elusive. In this work, taking human peripheral myelin protein 22 (PMP22) as an example, we employ coarse-grained molecular dynamics simulations to investigate the partitioning of both the natural PMP22 and the palmitoylated PMP22 (pal-PMP22) into the lipid domains of model myelin membranes. The results indicate that palmitoylation drives PMP22 to localize at the boundary of the liquid-ordered (Lo) and liquid-disordered (Ld) domains and increases the possibility of PMP22 partitioning into the Lo domains by changing the hydrophobic length of the proteins and perturbing the ordered packing of tails of the saturated lipids in the Lo domains. This work offers some novel insights into the role of palmitoylation in modulating the function of membrane proteins in cellular membranes.
Fund: Project supported by Zhejiang Provincial Natural Science Foundation of China (Grant No. LZ25A040005) and the National Natural Science Foundation of China (Grant No. 11674287).
Shishi Wu(吴施施) and Qing Liang(梁清) Effects of palmitoylation on membrane protein partitioning into lipid domains in model cellular membranes 2025 Chin. Phys. B 34 058701
[1] Sezgin E, Levental I, Mayor S and Eggeling C 2017 Nat. Rev. Mol. Cell Biol. 18 361 [2] Singer S J and Nicolson G L 1972 Science 175 720 [3] Simons K and Ikonen E 1997 Nature 387 569 [4] Ingólfsson H I, Melo M N, van Eerden F J, Arnarez C, Lopez C A, Wassenaar T A, Periole X, de Vries A H, Tieleman D P and Marrink S J 2014 J. Am. Chem. Soc. 136 14554 [5] Levental I and Lyman E 2023 Nat. Rev. Mol. Cell Biol. 24 107 [6] Goyette J and Gaus K 2017 Curr. Opin. Cell Biol. 44 86 [7] Garcia-Parajo M F, Cambi A, Torreno-Pina J A, Thompson N and Jacobson K 2014 J. Cell Sci. 127 4995 [8] Puff N 2023 Membranes 13 652 [9] Moreno-Pescador G, Arastoo M R, Ruhoff V T, Chiantia S, Daniels R and Bendix P M 2023 Nano Lett. 23 3377 [10] Kusumi A, Fujiwara T K, Tsunoyama T A, Kasai R S, Liu A A, Hirosawa K M, Kinoshita M, Matsumori N, Komura N, Ando H and Suzuki K G N 2020 Traffic 21 106 [11] Lin X and Gorfe A A 2019 J. Phys. Chem. B 123 1009 [12] Lorent J H, Diaz-Rohrer B, Lin X, Spring K, Gorfe A A, Levental K R and Levental I 2017 Nat. Commun. 8 1219 [13] Lin X, Gorfe A A and Levental I 2018 Biophys. J. 114 1936 [14] Balakrishnan M and Kenworthy A K 2024 J. Am. Chem. Soc. 146 1374 [15] Jetten A M and Suteri U 2000 Prog. Nucleic Acid Res. Mol. Biol. 64 97 [16] Snipes G J, Suter U, Welcher A A and Shooter E M 1992 J. Cell Biol. 117 225 [17] Zhou Y, Miles J R, Tavori H, Lin M, Khoshbouei H, Borchelt D R, Bazick H, Landreth G E, Lee S, Fazio S and Notterpek L 2019 J. Neurosci. 39 5404 [18] Stefanski K M, Wilkinson M C and Sanders C R 2024 Biochem. So. Trans. 52 1747 [19] Prior R, Silva A, Vangansewinkel T, et al. 2024 Brain 147 3113 [20] van Paassen B W, van der Kooi A J, van Spaendonck-Zwarts K Y, Verhamme C, Baas F and de Visser M 2014 Orphanet. J. Rare Dis. 9 38 [21] Attarian S, Fatehi F, Rajabally Y A and Pareyson D 2020 J. Neurol. 267 2198 [22] Taioli F, Cabrini I, Cavallaro T, Acler M and Fabrizi G M 2011 Brain 134 608 [23] Li J, Parker B, Martyn C, Natarajan C and Guo J 2013 Mol. Neurobiol. 47 673 [24] Saher G, Brügger B, Lappe-Siefke C, Möbius W, Tozawa R, Wehr M C, Wieland F, Ishibashi S and Nave K A 2005 Nat. Neurosci. 8 468 [25] Gopalakrishnan G, Awasthi A, Belkaid W, De Faria O, Liazoghli D, Colman D R and Dhaunchak A S 2013 J. Neurosci. Res. 91 321 [26] Marinko J T, Kenworthy A K and Sanders C R 2020 Proc. Natl. Acad. Sci. USA 117 14168 [27] Schlebach J P, Narayan M, Alford C, Mittendorf K F, Carter B D, Li J and Sanders C R 2015 J. Am. Chem. Soc. 137 8758 [28] Lee S, Amici S, Tavori H, Zeng W M, Freeland S, Fazio S and Notterpek L 2014 J. Neurosci. 34 16140 [29] Mittendorf K F, Marinko J T, Hampton C M, Ke Z, Hadziselimovic A, Schlebach J P, Law C L, Li J, Wright E R and Sanders C R 2017 Sci. Adv. 3 e1700220 [30] Zoltewicz S J, Lee S, Chittoor V G, Freeland S M, Rangaraju S, Zacharias D A and Notterpek L 2012 ASN Neuro. 4 [31] Li S, Li J, Ning L, Wang S, Niu Y, Jin N, Yao X, Liu H and Xi L 2015 J. Chem. Inf. Model 55 2015 [32] Schlebach J P, Barrett P J, Day C A, Kim J H, Kenworthy A K and Sanders C R 2016 Biochemistry 55 985 [33] Wang T Y, Leventis R and Silvius J R 2001 Biochemistry 40 13031 [34] Uchida K, Obayashi H, Minamihata K, Wakabayashi R, Goto M, Shimokawa N, Takagi M and Kamiya N 2022 Langmuir 38 9640 [35] Marrink S J, Corradi V, Souza P C T, Ingólfsson H I, Tieleman D P and Sansom M S P 2019 Chem. Rev. 119 6184 [36] Marrink S J, Risselada H J, Yefimov S, Tieleman D P and de Vries A H 2007 J. Phys. Chem. B 111 7812 [37] Borges-Araújo L, Borges-Araújo A C, Ozturk T N, Ramirez- Echemendia D P, Fábián B, Carpenter T S, Thallmair S, Barnoud J, Ingólfsson H I, Hummer G, Tieleman D P, Marrink S J, Souza P C T and Melo M N 2023 J. Chem. Theory Comput. 19 7387 [38] Souza P C T, Alessandri R and Barnoud J, et al. 2021 Nat. Methods 18 382 [39] Wu Q Y and Liang Q 2014 Langmuir 30 1116 [40] Lin X, Chen X J and Liang Q 2021 Chin. Phys. B 30 068701 [41] Chen X J and Liang Q 2017 Chin. Phys. B 26 048701 [42] Chen J, Tieleman D P and Liang Q 2022 J. Phys. Chem. Lett. 13 991 [43] de Jong D H, Singh G, Bennett W F, Arnarez C, Wassenaar T A, Schäfer L V, Periole X, Tieleman D P and Marrink S J 2013 J. Chem. Theory Comput. 9 687 [44] Lin X, Chen X J and Liang Q 2021 Chin. Phys. B 30 068701 [45] Chen X J and Liang Q 2017 Chin. Phys. B 26 048701 [46] Jo S, Kim T, Iyer V G and Im W 2008 J. Comput. Chem. 29 1859 [47] Koukos P I, Dehghani-Ghahnaviyeh S, Velez-Vega C, Manchester J, Tieleman D P, Duca J S, Souza P C T and Cournia Z 2023 J. Chem. Theory Comput. 19 8901 [48] Wassenaar T A, Ingólfsson H I, Böckmann R A, Tieleman D P and Marrink S J 2015 J. Chem. Theory Comput. 11 2144 [49] Li W, Lin Z, Yuan B and Yang K 2020 Chin. Phys. B 29 128701 [50] Abraham M J, Murtola T, Schulz R, Páll S, Smith J C, Hess B and Lindahl E 2015 SoftwareX 1 19 [51] Bussi G, Donadio D and Parrinello M 2007 J. Chem. Phys. 126 014101 [52] Berendsen H J C, Postma J P M, van Gunsteren W F, DiNola A and Haak J R 1984 J. Chem. Phys. 81 3684 [53] Park S, YeomMS, Andersen O S, Pastor R W and Im W 2019 J. Chem. Theory Comput. 11 6491 [54] Domański J, Hedger G, Best R B, Stansfeld P J and Sansom M S P 2016 J. Phys. Chem. B 121 3364 [55] Souaile M and Roux B 2001 Comput. Phys. Commun. 135 40 [56] Hub J S, de Groot B L and van der Spoel D 2010 J. Chem. Theory Comput. 6 3713 [57] Efron B 1979 Ann. Statist. 7 1 [58] Zhu F and Hummer G 2012 J. Comput. Chem. 33 453 [59] Humphrey W, Dalke A and Schulten K 1996 J. Mol. Graph 14 33 [60] Kim T and Im W 2010 Biophys. J. 99 175 [61] Andersen O S and Koeppe R E II 2007 Annu. Rev. Biophys. Biomol. Struct. 36 107 [62] Liang Q, Wu Q Y and Wang Z Y 2014 J. Chem. Phys. 141 074702
Altmetric calculates a score based on the online attention an article receives. Each coloured thread in the circle represents a different type of online attention. The number in the centre is the Altmetric score. Social media and mainstream news media are the main sources that calculate the score. Reference managers such as Mendeley are also tracked but do not contribute to the score. Older articles often score higher because they have had more time to get noticed. To account for this, Altmetric has included the context data for other articles of a similar age.