Brefeldin A

• γ ,4- dihydroxy-2- (6 -hydroxy-1 - heptenyl )-4- cyclopentanecrotonic Acid λ -lactone

White to yellow white crystalline powder

Fixed

Risk

275 mg · kg -1 ( LD50, rat, oral)

Template: Infobox chemical / molecular formula search available

Brefeldin A (abbreviation: BFA) is a lactone antibiotic that is synthesized by fungi such as Eupenicillium brefeldianum and was originally isolated as an antiviral agent. Today it is mainly used in medical and biological research for the investigation of protein transport.

BFA induced retrograde transport from the Golgi apparatus to the endoplasmic reticulum, resulting in the accumulation of proteins ( for example, interferon γ ) in the endoplasmic reticulum. Brefeldin A seems to thereby engage a particular GTP exchange factor that is responsible for the activation of the GTPase Arf1p.

Physical Properties

Solubility in water:

• Clear, colorless solution in 10 mg / ml of dichloromethane.
• Clear, colorless solution in 10 mg / ml of methanol.

The effect of brefeldin A

Brefeldin A acts in a very short time as a cell poison: The Golgi apparatus breaks down and turns to the endoplasmic reticulum ( ER). Because of these characteristics Brefeldin is a potent inhibitor of the secretion of a cell: proteins to be secreted, are translated in the ER, mature in the Golgi and post-Golgi compartments and are eventually released by vesicle fusion with the cell membrane.

Brefeldin A inhibits proteins that activate ADP- ribosylation factors, the so-called Arf. ER are organized by small GTP - G proteins loaded ARF family protein complexes called coats. The Coats help you select the necessary transport molecules and act as a scaffold, are pinched off at the vesicle. On the way from the ER to the Golgi towards such vesicles are only cut off from the ER and then incorporated into the Golgi ( anterograde transport or maturation cistern ); be reversed in the same way, proteins in vesicles for reuse from the Golgi back to the ER funneled ( retrograde transport ). The formation of such vesicles depends on the COP -I on storage by Arf1 -GTP from. Brefeldin A inhibition of Arf1 triggers the COP -I vesicles, can collapse the Golgi and stores the affected proteins back into the ER.

By GTP -cleaving GTPase active Arf1 -GTP is converted to the inactive Arf1 -GDP. Arf1 - GPD in turn exchanges mediated by GDP- Sec7 - GTP exchange factors, GDP for GTP from again. Brefeldin A blocks the GDP- GTP exchange by the Arf1 - GPD: Sec7 complex stabilized and thus inactivated. This was the first example that a toxin begins a protein in a trap, eliminating its function.