ESF Eurocores SONS Project NanoSMAP

Membrane Proteins Explained

Each cell in the body is surrounded by a cell membrane. In fact, organelles (the functional subunits within a cell) are separately enclosed by their own membrane. These cell membranes, also called a lipid bilayers, contain many different types of molecules, including proteins which are involved in a processes such as cell signalling, cell adhesion, ion channel conductance, transport of molecules in and out of each cell, and more.

Examples of Membrane Proteins

The membrane proteins are proteins embedded in the cell membrane or associated with the cell membranes in some way. These proteins are essential to the functioning of the cells and thus to our health. Cell surface receptors comprise a vast number of structurally diverse membrane proteins such as G-protein-coupled receptors (GPCRs), ion channels, transporters and aquaporins just to mention a few. Understanding cellular signalling mediated by cell surface receptors is in the focus of present biological research and central for drug development. Some membrane proteins act as senders or receivers of signals between cells. Other proteins act as markers allowing cells to identify a cell to other cells. These communication and identification systems form the basis of all cell-to-cell interaction in the immune system. Other membrane proteins are transporters, moving sugar, amino acids, ions and water in and out of the cells as needed. About a third of all proteins in the body are membrane proteins.

The Role of Membrane Proteins in Disease

Because the membrane proteins are responsible for so many vital functions of the cells, it is easy to see why any dysfunction of these proteins might cause disease. Ths is also why the membrane proteins have become prime drug targets. Today, more than 50% of all drug targets are membrane proteins, and that number is expected to rise as more is understood about the workings of the membrane proteins.

When membrane proteins cause disease, it may be due to over- or underfunction of the protein(s) involved. There may not be enough of the protein produced by the body, or too much is produced. Or, either too much or not enough of the protein be "switched on" to adequately perform thefunctions it is supposed to carry out. Genetic mutations, autoimmune attack, or drug treatment that perturbs cellular function are some factors that may cause dysfunction of membrane proteins. Such dysfunction of the ion channel proteins are the cause of, for example, Cystic Fibrosis, several types of epilepsy, migraines, cardiac arrythmias, and more. Protein misfolding (e.g., proteins failing to acquire or re-acquire their functional state or structure) and aggregation may also cause disease, for example Alzheimer's, Parkinson's, Huntington's, Creutzfeldt-Jakobs (CJD) and many cancers.

It is already known that factors such as ionic strength, pH and temperature, among other factors, may influence protein folding. The ASMENA project will study and model the influences of such factors on biochemical interactions on the structure of the lipid bilayer and the membrane proteins.

As yet, very little is understood about membrane proteins compared to other structures in the body. For example, more gene sequences are known that protein structures. Membrane proteins are difficult to crystallize and thus it is particularly difficult to determine their structure. Also, the membrane proteins will not function or have the correct structure unless they are part of a lipid membrane of (more or less) the right kind. This means that virtually all analytical methods available today to understand proteins by analyzing their structure (which require crystals of the protein in its correct structure) and measure how various drug compounds bind to them and change their function does not work. For correct readouts, the protein must be recreated in a suitable lipid membrane, in a configuration suitable for measuring. The aim of the ASMENA project is to develop tools and techniqes which allow for measurements on self-assembled lipid bilayers (membranes) on chips ("lab on a chip").

Read more about ion channels here.

Read more about aquaporins here.

Read more about GPCRs here.

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