Biology Reference
In-Depth Information
Several of the mitochondrial electron transport/oxidative phosphorylation complexes
have been shown to require CL in order to maintain full enzymatic function. Examples
include Complex IV (cytochrome c oxidase) that requires 2 CLs, Complex III (cytochrome
bc1) and Complex V (F1 ATPase) that requires 4 CLs. While all of these various examples
clearly indicate an important role for CL in mitochondrial bioenergetics, no absolute speci-
ficity has yet been demonstrated. Mitochondrial function can be maintained by PC without
CL, albeit at reduced levels and the activity ratio for CL-PC is only about 5.
4. Hydrophobic Match
One partial explanation for the large number of membrane lipid species ('lipid diversity')
is the requirement for lipids of different lengths to properly solvate the varying hydrophobic
surface areas associated with integral membrane proteins. Relationship between length of the
trans-membrane protein hydrophobic surface and the hydrophobic thickness of the neigh-
boring lipid bilayer is referred to as the 'hydrophobic match'
[66,67]
. A basic assumption
is that these two lengths should be similar and if they are not, the mismatch must be compen-
sated for by alterations in lipid and/or protein structure.
It has been shown that size of the hydrophobic segment on the membrane protein varies
from protein to protein even within the same membrane and the length of the lipid bilayer
hydrophobic interior varies with the lipid shape, acyl chain length, and number and location
of any double bonds. Temperature, lateral pressure, cholesterol content, and presence of
divalent metal ions can also affect thickness of the bilayer. A major membrane bilayer 'thick-
ening' agent is cholesterol. Cholesterol-rich domains, including lipid rafts, are partially char-
acterized by being significantly thicker than the neighboring non-raft bilayer. In proteins, the
hydrophobic trans-membrane segments are related to the types and sequence of the amino
acids comprising the segment. Of particular importance is the number of trans-membrane
a
-helices present. As a result, the hydrophobic match length may vary considerably. For
example, in E. coli, the hydrophobic length of the inner membrane leader peptidase is 15
amino acids long while the lactose permease is 24
4 amino acids long. Lipids can affect
protein activity, stability, orientation, state of aggregation, localization, and conformation.
Proteins in turn can affect lipid chain order, phase transition, phase behavior, and microdo-
main formation. Therefore, simultaneously lipids can affect membrane integral proteins and
integral proteins can affect nearby membrane lipids. The effect of hydrophobic mismatch
must be concurrently viewed from the perspective of both the lipid and the protein.
The Hydrophobic Match Length: A DSC Study
Determining the hydrophobic match length is not a straightforward measurement.
Although X-ray crystallography can determine the precise location of every atom in a protein,
it cannot identify with any certainty the location of the hydrophobic span that would accom-
modate the lipid bilayer. One unusual and indirect method that has been used to determine
the length of the hydrophobic match involves differential scanning calorimetry (DSC) (see
Chapter 9). In one report, Toconne and collaboraters
[68]
reconstituted bacteriorhodopsin iso-
lated from Halobacterium halobium into lipid bilayers composed of phosphatidylcholines
(PCs) containing acyl chains of different lengths. The PCs were dilauroyl PC (DLPC,
12:0,12:0 PC), dimyristoyl PC (DMPC, 14:0,14:0 PC), dipalmitoyl PC (16:0,16:0 PC), and
