Biology Reference
In-Depth Information
bacteriorhodopsin at 3.1
3.2 nm. This experiment supports some important basic conclu-
sions. First, proteins of the same hydrophobic match length can be accommodated into bila-
yers of different thickness and integral proteins can severely affect neighboring lipid
structure.
Single span
e
a
-helices are particularly sensitive to hydrophobic mismatch
[66
70]
. If length
e
of the trans-membrane
-helix exceeds the bilayer hydrophobic thickness, the helix may tilt
to shorten its effective length, or it may bend or even slightly compress or may adjust its
conformation into a different type of helix altogether. An incorrect helix length may cause
the protein to aggregate. If the helix is much too short, the protein may even be excluded
from the membrane interior, resulting in a new surface location. Multiple span proteins
are resistant to tilt and it is hard to assess the size and importance of mismatch. For example,
it has been reported that the multi-span protein rhodopsin needs a substantial lipid mismatch
of 4
˚
thicker or 10
˚
thinner than the protein's hydrophobic length in order to aggregate.
It is likely that all integral proteins may select lipids of appropriate match length from the
myriad of lipids that comprise the surrounding bilayer. Many, perhaps most, of the bilayer
lipids have a cone-shape and so prefer non-lamellar structure. The presence of can-shaped
lipids stabilizes the lamellar structure, but the presence of so many cone-shaped lipids
puts the lamellar bilayer under stress. This is referred to as a 'frustrated bilayer' that is
susceptible to factors that may drive the bilayer into non-lamellar structure. Among these
factors are proteins exhibiting a hydrophobic mismatch.
a
Biological Function of the Hydrophobic Match
Many studies have linked protein activity to hydrophobic mismatch
[66,67]
. A good
example comes from the (Ca
2
þ
þ
Mg
2
þ
)-ATPase isolated from the sarcoplasmic reticulum
[71]
. The enzyme was reconstituted into bilayers made from PCs with monounsaturated
(cis
D
9) chains of length n
¼
12 to n
¼
23. Enzyme activity increased from n
¼
12 to
n
23. Mixtures of any of these two lipids supported an activity
that was the average of the two lipids. Also, the addition of decane to n
¼
20, then decreases for n
¼
¼
12 increased
activity. This experiment indicates that biological activity of the (Ca
2
þ
þ
Mg
2
þ
)-ATPase
was maximal at a hydrophobic match length of 18
20 carbons. These same investigators later
reported similar findings for the reconstituted Na
þ
,K
þ
ATPase
[72]
.
Biological membrane thickness, and hence hydrophobic match length, is now believed to
play a crucial role in membrane trafficking. In biological membranes, cholesterol content and
membrane thickness increase from the endoplasmic reticulum to the Golgi, and finally to the
plasma membrane. The average plasma membrane protein's hydrophobic match length is
a full 5 amino acids longer than those of the Golgi. It is believed that proteins with a shorter
hydrophobic match remain in the Golgi, while proteins with a longer hydrophobic match are
transported to the plasma membrane. Therefore the plasma membrane is much thicker than
the endoplasmic reticulum due to its high cholesterol and SM content, central components of
lipid rafts.
A different type of hydrophobic match occurs between membrane lipids, the best docu-
mented being between cholesterol and phospholipid acyl chains. Decades ago it was noted
that the rigid ring structure of cholesterol fitted nicely next to a stretch of nine saturated
carbons from acyl chain C-1 to C-9. Interruption of this stretch by a double bond decreases
cholesterol affinity. Therefore cholesterol interacts well with long saturated fatty acyl chains
e
