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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

A simplified drawing representing the various interactions of proteins with lipid bilayers as a function of time:1, a peripheral or extrinsic protein; 2, an integral or intrinsic protein; 3, a non-permanent protein that interacts reversibly with the membrane, a lipid-transfer protein in this particular example; 4, a non-permanent protein that becomes irreversibly bound to the bilayer once it interacts with it; 5, a non-permanent protein reversibly bound to a secretion vesicle and then transferred to a target membrane. A, B and C correspond to consecutive stages in the interaction process.
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fig01: A simplified drawing representing the various interactions of proteins with lipid bilayers as a function of time:1, a peripheral or extrinsic protein; 2, an integral or intrinsic protein; 3, a non-permanent protein that interacts reversibly with the membrane, a lipid-transfer protein in this particular example; 4, a non-permanent protein that becomes irreversibly bound to the bilayer once it interacts with it; 5, a non-permanent protein reversibly bound to a secretion vesicle and then transferred to a target membrane. A, B and C correspond to consecutive stages in the interaction process.

Mentions: Membrane-spanning (integral, intrinsic) proteins are permanently embedded in the lipid bilayer (Fig. 1). In many cases, the type of lipids that interact with amino acids in the hydrophobic environment of the membrane core and those at the interface are more or less defined, and to a certain extent regulated by the features of the protein. Transmembrane proteins also influence lipid structure in the membrane. Therefore, it is not surprising that changes in the lipid environment of membranes regulate or alter the function of intrinsic membrane proteins (see below). Indeed, in regions rich in a given type of receptor (e.g. synaptosomes, receptor clusters, etc.) these protein-lipid interactions play important roles in both directions.


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)

A simplified drawing representing the various interactions of proteins with lipid bilayers as a function of time:1, a peripheral or extrinsic protein; 2, an integral or intrinsic protein; 3, a non-permanent protein that interacts reversibly with the membrane, a lipid-transfer protein in this particular example; 4, a non-permanent protein that becomes irreversibly bound to the bilayer once it interacts with it; 5, a non-permanent protein reversibly bound to a secretion vesicle and then transferred to a target membrane. A, B and C correspond to consecutive stages in the interaction process.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4401130&req=5

fig01: A simplified drawing representing the various interactions of proteins with lipid bilayers as a function of time:1, a peripheral or extrinsic protein; 2, an integral or intrinsic protein; 3, a non-permanent protein that interacts reversibly with the membrane, a lipid-transfer protein in this particular example; 4, a non-permanent protein that becomes irreversibly bound to the bilayer once it interacts with it; 5, a non-permanent protein reversibly bound to a secretion vesicle and then transferred to a target membrane. A, B and C correspond to consecutive stages in the interaction process.
Mentions: Membrane-spanning (integral, intrinsic) proteins are permanently embedded in the lipid bilayer (Fig. 1). In many cases, the type of lipids that interact with amino acids in the hydrophobic environment of the membrane core and those at the interface are more or less defined, and to a certain extent regulated by the features of the protein. Transmembrane proteins also influence lipid structure in the membrane. Therefore, it is not surprising that changes in the lipid environment of membranes regulate or alter the function of intrinsic membrane proteins (see below). Indeed, in regions rich in a given type of receptor (e.g. synaptosomes, receptor clusters, etc.) these protein-lipid interactions play important roles in both directions.

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