Targeting
by tail-anchor sequences occurs by two
different mechanisms.
The blue protein is targeted by a
receptor mediated ATP dependent mechanism. The green
protein is targeted by a conformational change that occurs in
the cytoplasm.
Tail-anchors are hydrophobic sequences located at the carboxyl-terminus
of a variety of functionally unrelated protein. These sequences
serve to target the protein to the appropriate subcellular membrane as well as
to anchor it into the lipid bilayer
A) Receptor mediated, ATP dependent, targeting. This pathway
is used by Vamp proteins, Sec61b
and g,
and several proteins targeted initially to the endoplasmic
reticulum and that are then sorted throughout the secretory pathway.
B) Spontaneous insertion does not require ATP. Bcl-2 family
proteins, cytochrome b5 and Acta are all targeted
by a mechanism that involves an equilibrium in the cytoplasm that competes with membrane
assembly. At least in the case of Bax it appears that the equilibrium in the
cytoplasm is between insertion competent and insertion blocked
conformations. Etoposide
leads the cell to trigger a conformational change in Bax
that causes it to insert into mitochondria and ER early during
apoptosis.(Kim
PK et al Biochemistry. 1997)
Because they are so close to the
carboxyl-terminus the tail-anchor is still inside the ribosome when
translation of the protein finishes. Therefore, these proteins must be
targeted to membranes post-translationally. There are two known mechanisms
for targeting these protein (A and B above).
