Öjemalm Karin, Higuchi Takashi, Lara Patricia, Lindahl Erik, Suga Hiroaki, von Heijne Gunnar
Department of Biochemistry and Biophysics, Center for Biomembrane Research, Stockholm University, SE-106 91 Stockholm, Sweden;
Department of Chemistry, Graduate School of Science, University of Tokyo, 113-0033 Tokyo, Japan;
Proc Natl Acad Sci U S A. 2016 Sep 20;113(38):10559-64. doi: 10.1073/pnas.1606776113. Epub 2016 Sep 6.
Cotranslational translocon-mediated insertion of membrane proteins into the endoplasmic reticulum is a key process in membrane protein biogenesis. Although the mechanism is understood in outline, quantitative data on the energetics of the process is scarce. Here, we have measured the effect on membrane integration efficiency of nonproteinogenic analogs of the positively charged amino acids arginine and lysine incorporated into model transmembrane segments. We provide estimates of the influence on the apparent free energy of membrane integration (ΔGapp) of "snorkeling" of charged amino acids toward the lipid-water interface, and of charge neutralization. We further determine the effect of fluorine atoms and backbone hydrogen bonds (H-bonds) on ΔGapp These results help establish a quantitative basis for our understanding of membrane protein assembly in eukaryotic cells.
共翻译转位子介导的膜蛋白插入内质网是膜蛋白生物合成中的一个关键过程。尽管该机制的大致情况已为人所知，但关于该过程能量学的定量数据却很稀少。在这里，我们测量了掺入模型跨膜片段中的带正电荷氨基酸精氨酸和赖氨酸的非蛋白质ogenic类似物对膜整合效率的影响。我们提供了关于带电荷氨基酸向脂质-水界面“ snorkeling”以及电荷中和对膜整合表观自由能（ΔGapp）影响的估计。我们进一步确定了氟原子和主链氢键（H键）对ΔGapp的影响。这些结果有助于为我们理解真核细胞中的膜蛋白组装建立定量基础。
