期刊
BIOPHYSICAL CHEMISTRY
卷 291, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.bpc.2022.106907
关键词
Signal peptide; Apolipoprotein E; Cholesterol
资金
- Science and Technology Department, Government of Odisha, Core Research Grant of Science and Engineering Research Board (SERB) [CRG/2021/001515]
- SERB -Science and Technology Award [STR/2021/000029]
- Science and Engineering Research Board (SERB), DST [CRG/2021/002239]
This study reveals that the signal peptide of proteins has a preference for the lipid composition of membranes during protein trafficking, with cholesterol playing a key role. This property can be utilized for the development of organelle-specific cargo delivery.
Soluble secretory and membrane proteins contain a short stretch of signal peptide (SP) at their N-terminal end, which gets cleaved after reaching the destination organelle. However, the importance of SP in protein trafficking is not fully understood. The lipid compositions of cellular organelles are highly heterogeneous, and the prefer-ence of SP toward a particular lipid composition might play a key role in unidirectional trafficking of protein. In order to understand the preference of Apolipoprotein E (ApoE) toward endoplasmic reticulum (ER), we have studied the interaction of its SP with membranes of varying lipid compositions. The importance of cholesterol is paramount as subcellular organelles contain differential amount of cholesterol; endoplasmic reticulum (ER) contains the least amount of cholesterol. We have utilized batteries of steady-state and time-resolved fluores-cence techniques to understand the affinity of ApoE signal peptide toward membranes of varying lipid compo-sitions. We observed that the ApoE signal peptide binds tightly with membranes devoid of cholesterol, and binding affinity reduces with increasing concentration of membrane cholesterol. Our results clearly suggest the importance of membrane composition in the unidirectional movement of ApoE toward ER. This property of SP can further be utilized for the development of organelle specific cargo delivery.
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