Myristoylation versus SRP
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《细胞学杂志》
b5R is a flavoprotein with two homes: one in the ER membrane, where it functions in lipid metabolism, and another in the mitochondrial outer membrane (MOM), where it regenerates reduced ascorbate. b5R is myristoylated in both locations. But the modification is only required for the mitochondrial targeting, as mutation of the myristoylation site confines b5R to the ER.
The new article reveals that b5R's dual localization relies on a fine balance between N-myristoylation and capture by the signal recognition particle (SRP), which bound to b5R's NH2-terminal membrane-anchoring region. This binding was weak, however, and was further weakened by myristoylation. The modification caused a conformational change in b5R's NH2-terminal region that may lower but not eliminate its affinity for SRP. By partly avoiding the ER, b5R is available for insertion into the MOM.
A longer, more hydrophobic anchor, which has a higher affinity for SRP, disrupted MOM targeting and decreased myristoylation. Most of this b5R was found at the ER.
The findings show the importance of weak targeting signals for dual localization. When more of the b5R is needed in the ER, cells could either up-regulate SRP or down-regulate the myristoylation machinery.(The machineries for myristoylation and c)
The new article reveals that b5R's dual localization relies on a fine balance between N-myristoylation and capture by the signal recognition particle (SRP), which bound to b5R's NH2-terminal membrane-anchoring region. This binding was weak, however, and was further weakened by myristoylation. The modification caused a conformational change in b5R's NH2-terminal region that may lower but not eliminate its affinity for SRP. By partly avoiding the ER, b5R is available for insertion into the MOM.
A longer, more hydrophobic anchor, which has a higher affinity for SRP, disrupted MOM targeting and decreased myristoylation. Most of this b5R was found at the ER.
The findings show the importance of weak targeting signals for dual localization. When more of the b5R is needed in the ER, cells could either up-regulate SRP or down-regulate the myristoylation machinery.(The machineries for myristoylation and c)