Biology Reference
In-Depth Information
interaction. Thus, bivariate correlation functions based on both orientation and po-
sition of lipid tails around cholesterol molecules have been used in the recent years to
define the amount and the preferential interaction sites of phospholipids around cho-
lesterol in 2 (
Martinez-Seara, R´g, Karttunen, Vattulainen, &Reigada, 2010
) or even
3 dimensions (
Pitman, Suits, Mackerell, & Feller, 2004
).
Apart from membrane structure, biophysical parameters describing the lateral
motion of lipids and proteins are needed for a more complete characterization of
the membrane system under study. Values of root mean square displacement and dif-
fusion coefficients serve as a reference of how changes in membrane composition
affect membrane dynamics. We do not have, however, the computational power
needed to generate reliable data on protein or lipid diffusion. On the one hand, all
current models still lack the adequate level of representation or the necessary time-
scale for an accurate interpretation (
Javanainen et al., 2013
). On the other hand, var-
ious studies point towards an existing concerted diffusion in membrane (
Apajalahti
et al., 2010
) and membrane-protein systems (
Niemel
¨
et al., 2010
). As a result, the
interpretation of diffusion data on lipid or protein diffusion needs to be used with
extreme caution.
4.2
GPCR MONOMERS IN MEMBRANES
The relationship between lipids and GPCRs is today a well-known fact. The GPCR
surface is the most common and intuitive place of interaction between the lipids and
GPCRs. Although such interaction has been always thought to be unspecific, various
studies describe certain specificity between cholesterol and GPCRs (
Thompson
et al., 2011
). On the one hand, cholesterol seems to affect the GPCR architecture
and various specific interaction sites have been postulated (
Cang et al., 2013;
Sengupta & Chattopadhyay, 2012
).
Hanson et al. (2008)
have recently described
for the first time a specific cholesterol binding site at the crystal structure of the
b
2
-adrenergic receptor. The authors even define what they call a cholesterol consensus
motif present in most of the class A GPCRs. Membrane phospholipids also seem to
interact to a certain extent with the surface of GPCRs. Both computational (
Pitman,
Grossfield, Suits, & Feller, 2005
) and experimental (
Gawrisch, Soubias, &
Mihailescu, 2008
) works show how preferential interactions between GPCRs and
membrane phospholipids are linked to the degree of chain unsaturation of the mem-
brane. A well-known interaction between lipids and GPCRs, although only occurring
within the Golgi apparatus, is the so-called palmitoylation. GPCR palmitoylation is a
posttranslational modification that many GPCRs undergo during their process of mat-
uration. A palmitic acid is covalently linked to one or more cysteines of the GPCR,
increasing its hydrophobicity and driving it to membrane and subcellular localization
(
Goddard & Watts, 2012
). Without a doubt, the most intimate relationship between
lipids and GPCRs ever crystallized can be observed, however, at the recent structure
of the sphingosine-1-phosphate receptor (
Parrill, Lima, & Spiegel, 2012
). This recep-
tor can accommodate a physiological phosphosphingolipid in its binding pocket, in
