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Membranes: a meeting point for lipids, proteins and therapies.

Escribá PV, González-Ros JM, Goñi FM, Kinnunen PK, Vigh L, Sánchez-Magraner L, Fernández AM, Busquets X, Horváth I, Barceló-Coblijn G - J. Cell. Mol. Med. (2008)

Bottom Line: Moreover, their alteration has been associated with the development of numerous diseases.The present study reviews these interactions from the molecular and biomedical point of view, and the effects of their modulation on the physiological activity of cells, the aetiology of human diseases and the design of clinical drugs.In fact, the influence of lipids on protein function is reflected in the possibility to use these molecular species as targets for therapies against cancer, obesity, neurodegenerative disorders, cardiovascular pathologies and other diseases, using a new approach called membrane-lipid therapy.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Molecular Cell Biomedicine, Dept of Biology-IUNICS, University of the Balearic Islands, Palma de Mallorca, Spain. pablo.escriba@uib.es

ABSTRACT
Membranes constitute a meeting point for lipids and proteins. Not only do they define the entity of cells and cytosolic organelles but they also display a wide variety of important functions previously ascribed to the activity of proteins alone. Indeed, lipids have commonly been considered a mere support for the transient or permanent association of membrane proteins, while acting as a selective cell/organelle barrier. However, mounting evidence demonstrates that lipids themselves regulate the location and activity of many membrane proteins, as well as defining membrane microdomains that serve as spatio-temporal platforms for interacting signalling proteins. Membrane lipids are crucial in the fission and fusion of lipid bilayers and they also act as sensors to control environmental or physiological conditions. Lipids and lipid structures participate directly as messengers or regulators of signal transduction. Moreover, their alteration has been associated with the development of numerous diseases. Proteins can interact with membranes through lipid co-/post-translational modifications, and electrostatic and hydrophobic interactions, van der Waals forces and hydrogen bonding are all involved in the associations among membrane proteins and lipids. The present study reviews these interactions from the molecular and biomedical point of view, and the effects of their modulation on the physiological activity of cells, the aetiology of human diseases and the design of clinical drugs. In fact, the influence of lipids on protein function is reflected in the possibility to use these molecular species as targets for therapies against cancer, obesity, neurodegenerative disorders, cardiovascular pathologies and other diseases, using a new approach called membrane-lipid therapy.

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Related in: MedlinePlus

Non-lamellar-prone lipids with a small polar head-group (e.g. phosphatidylethanolamine [PE], blue) induce the formation of non-lamellar-prone regions. These bilayers, with a frustrated (lɛ) lamellar phase, can be stabilized by proteins (green) or other lamellar-prone lipids (orange). The loose packing of these bilayers allows some acyl chains to exit the membrane plane and become located in hydrophobic protein sockets (upper scheme). Hydrophobic protein domains, which may correspond to amino acid sequences or lipid modifications, may also be inserted into the membrane. Therefore, non-lamellar-prone lipids facilitate the docking of amphitropic proteins to the membrane. One of these lipids, PE, is abundant in the inner monolayer of the plasma membrane where most peripheral proteins are found.
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fig02: Non-lamellar-prone lipids with a small polar head-group (e.g. phosphatidylethanolamine [PE], blue) induce the formation of non-lamellar-prone regions. These bilayers, with a frustrated (lɛ) lamellar phase, can be stabilized by proteins (green) or other lamellar-prone lipids (orange). The loose packing of these bilayers allows some acyl chains to exit the membrane plane and become located in hydrophobic protein sockets (upper scheme). Hydrophobic protein domains, which may correspond to amino acid sequences or lipid modifications, may also be inserted into the membrane. Therefore, non-lamellar-prone lipids facilitate the docking of amphitropic proteins to the membrane. One of these lipids, PE, is abundant in the inner monolayer of the plasma membrane where most peripheral proteins are found.

Mentions: Membranes are made up of molecules that to some extent preserve their individual characteristics and hence, the particular structure of these molecular bricks influences the structural properties of the membrane. In this context, phospholipids with a bulky polar head, such as phosphatidylcholine (PC), have a cylindrical molecular or effective shape and they tend to associate with other cylinder-like phospholipids to form planar structures [14, 15]. Other lipids might be prone to form non-bilayer structures. Cone-shaped lipids with bulky polar heads such as lysophosphatidylcholine (LPC), or truncated cone-shaped lipids with small headgroups such as phosphatidylethanolamine (PE), may form spherical micelles or tubular structures with positive (HI) or negative curvature (HII), respectively. Although these lipids form non-bilayer structures in membranes, the roles of which in general remain to be determined [13], in the last few years some functions have been attributed to non-bilayer prone lipids in planar structures (lipid bilayers). Indeed, these lipids appear to participate in the interaction of several proteins, such as, e.g. protein kinase C (PKC) with membranes [4]. Non-lamellar-prone membranes also favour the binding of heterotrimeric G proteins and Gβγ dimers, as well as displaying a lower binding affinity for Gα monomers [4–6]. The influence of non-lamellar-prone lipids in facilitating or regulating the docking of amphitropic membrane proteins may have originated from the interaction of a protein with membrane fatty acyl chains leaving the membrane plane, or through the insertion of a protein's hydrophobic domain into a bilayer with ‘loose' surface packing (Fig. 2) [16]. This is possibly due to the presence of HII-prone lipids, which generate ‘frustrated’ bilayers (lɛ phase) [15], which may be stabilized by interactions with proteins or lipids (Fig. 2) [9, 16]. Non-lamellar-prone lipids also participate in the formation of the cleavage furrow during cell cytokinesis [17], as well as in other membrane fission and fusion processes. Finally, membrane lipid heterogeneity is responsible for the distinct membrane regions, domains and microdomains that form the spatial organization of, which it is related to, the specific activity at the membrane.


Membranes: a meeting point for lipids, proteins and therapies.

Escribá PV, González-Ros JM, Goñi FM, Kinnunen PK, Vigh L, Sánchez-Magraner L, Fernández AM, Busquets X, Horváth I, Barceló-Coblijn G - J. Cell. Mol. Med. (2008)

Non-lamellar-prone lipids with a small polar head-group (e.g. phosphatidylethanolamine [PE], blue) induce the formation of non-lamellar-prone regions. These bilayers, with a frustrated (lɛ) lamellar phase, can be stabilized by proteins (green) or other lamellar-prone lipids (orange). The loose packing of these bilayers allows some acyl chains to exit the membrane plane and become located in hydrophobic protein sockets (upper scheme). Hydrophobic protein domains, which may correspond to amino acid sequences or lipid modifications, may also be inserted into the membrane. Therefore, non-lamellar-prone lipids facilitate the docking of amphitropic proteins to the membrane. One of these lipids, PE, is abundant in the inner monolayer of the plasma membrane where most peripheral proteins are found.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
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fig02: Non-lamellar-prone lipids with a small polar head-group (e.g. phosphatidylethanolamine [PE], blue) induce the formation of non-lamellar-prone regions. These bilayers, with a frustrated (lɛ) lamellar phase, can be stabilized by proteins (green) or other lamellar-prone lipids (orange). The loose packing of these bilayers allows some acyl chains to exit the membrane plane and become located in hydrophobic protein sockets (upper scheme). Hydrophobic protein domains, which may correspond to amino acid sequences or lipid modifications, may also be inserted into the membrane. Therefore, non-lamellar-prone lipids facilitate the docking of amphitropic proteins to the membrane. One of these lipids, PE, is abundant in the inner monolayer of the plasma membrane where most peripheral proteins are found.
Mentions: Membranes are made up of molecules that to some extent preserve their individual characteristics and hence, the particular structure of these molecular bricks influences the structural properties of the membrane. In this context, phospholipids with a bulky polar head, such as phosphatidylcholine (PC), have a cylindrical molecular or effective shape and they tend to associate with other cylinder-like phospholipids to form planar structures [14, 15]. Other lipids might be prone to form non-bilayer structures. Cone-shaped lipids with bulky polar heads such as lysophosphatidylcholine (LPC), or truncated cone-shaped lipids with small headgroups such as phosphatidylethanolamine (PE), may form spherical micelles or tubular structures with positive (HI) or negative curvature (HII), respectively. Although these lipids form non-bilayer structures in membranes, the roles of which in general remain to be determined [13], in the last few years some functions have been attributed to non-bilayer prone lipids in planar structures (lipid bilayers). Indeed, these lipids appear to participate in the interaction of several proteins, such as, e.g. protein kinase C (PKC) with membranes [4]. Non-lamellar-prone membranes also favour the binding of heterotrimeric G proteins and Gβγ dimers, as well as displaying a lower binding affinity for Gα monomers [4–6]. The influence of non-lamellar-prone lipids in facilitating or regulating the docking of amphitropic membrane proteins may have originated from the interaction of a protein with membrane fatty acyl chains leaving the membrane plane, or through the insertion of a protein's hydrophobic domain into a bilayer with ‘loose' surface packing (Fig. 2) [16]. This is possibly due to the presence of HII-prone lipids, which generate ‘frustrated’ bilayers (lɛ phase) [15], which may be stabilized by interactions with proteins or lipids (Fig. 2) [9, 16]. Non-lamellar-prone lipids also participate in the formation of the cleavage furrow during cell cytokinesis [17], as well as in other membrane fission and fusion processes. Finally, membrane lipid heterogeneity is responsible for the distinct membrane regions, domains and microdomains that form the spatial organization of, which it is related to, the specific activity at the membrane.

Bottom Line: Moreover, their alteration has been associated with the development of numerous diseases.The present study reviews these interactions from the molecular and biomedical point of view, and the effects of their modulation on the physiological activity of cells, the aetiology of human diseases and the design of clinical drugs.In fact, the influence of lipids on protein function is reflected in the possibility to use these molecular species as targets for therapies against cancer, obesity, neurodegenerative disorders, cardiovascular pathologies and other diseases, using a new approach called membrane-lipid therapy.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Molecular Cell Biomedicine, Dept of Biology-IUNICS, University of the Balearic Islands, Palma de Mallorca, Spain. pablo.escriba@uib.es

ABSTRACT
Membranes constitute a meeting point for lipids and proteins. Not only do they define the entity of cells and cytosolic organelles but they also display a wide variety of important functions previously ascribed to the activity of proteins alone. Indeed, lipids have commonly been considered a mere support for the transient or permanent association of membrane proteins, while acting as a selective cell/organelle barrier. However, mounting evidence demonstrates that lipids themselves regulate the location and activity of many membrane proteins, as well as defining membrane microdomains that serve as spatio-temporal platforms for interacting signalling proteins. Membrane lipids are crucial in the fission and fusion of lipid bilayers and they also act as sensors to control environmental or physiological conditions. Lipids and lipid structures participate directly as messengers or regulators of signal transduction. Moreover, their alteration has been associated with the development of numerous diseases. Proteins can interact with membranes through lipid co-/post-translational modifications, and electrostatic and hydrophobic interactions, van der Waals forces and hydrogen bonding are all involved in the associations among membrane proteins and lipids. The present study reviews these interactions from the molecular and biomedical point of view, and the effects of their modulation on the physiological activity of cells, the aetiology of human diseases and the design of clinical drugs. In fact, the influence of lipids on protein function is reflected in the possibility to use these molecular species as targets for therapies against cancer, obesity, neurodegenerative disorders, cardiovascular pathologies and other diseases, using a new approach called membrane-lipid therapy.

Show MeSH
Related in: MedlinePlus