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Chemical Synthesis of Native S-Palmitoylated Membrane Proteins through Removable-Backbone-Modification-Assisted Ser/Thr Ligation |
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| Authors: | Dong-Liang Huang Cédric Montigny Yong Zheng Veronica Beswick Ying Li Xiu-Xiu Cao Thomas Barbot Christine Jaxel Jun Liang Min Xue Chang-Lin Tian Nadège Jamin Ji-Shen Zheng |
| Affiliation: | 1. High Magnetic Field Laboratory, Chinese Academy of Sciences and Hefei National Laboratory for Physical Sciences at the Microscale, School of Life Sciences, University of Science and Technology of China, Hefei, 230027 China These authors contributed equally to this work.;2. Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Université Paris-Sud, Université Paris-Saclay, 91198 Gif-sur-Yvette cedex, France These authors contributed equally to this work.;3. Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Université Paris-Sud, Université Paris-Saclay, 91198 Gif-sur-Yvette cedex, France Department of Physics, Evry-Val-d'Essonne University, 91025 Evry, France;4. High Magnetic Field Laboratory, Chinese Academy of Sciences and Hefei National Laboratory for Physical Sciences at the Microscale, School of Life Sciences, University of Science and Technology of China, Hefei, 230027 China;5. Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Université Paris-Sud, Université Paris-Saclay, 91198 Gif-sur-Yvette cedex, France |
| Abstract: | The preparation of native S-palmitoylated (S-palm) membrane proteins is one of the unsolved challenges in chemical protein synthesis. Herein, we report the first chemical synthesis of S-palm membrane proteins by removable-backbone-modification-assisted Ser/Thr ligation (RBMGABA-assisted STL). This method involves two critical steps: 1) synthesis of S-palm peptides by a new γ-aminobutyric acid based RBM (RBMGABA) strategy, and 2) ligation of the S-palm RBM-modified peptides to give the desired S-palm product by the STL method. The utility of the RBMGABA-assisted STL method was demonstrated by the synthesis of rabbit S-palm sarcolipin (SLN) and S-palm matrix-2 (M2) ion channel. The synthesis of S-palm membrane proteins highlights the importance of developing non-NCL methods for chemical protein synthesis. |
| Keywords: | Chemische Proteinsynthese Membranproteine Ser/Thr-Ligation S-Palmitoylierung |