Membrane proteins and membrane receptors

Membrane proteins have diverse functions. Some of them consolidate the structure of the membrane, whereas others have more active functions, such as recognition (hormone, neurotransmitter and antibody receptors), pumping (ATPases), regulation of the inflow of ions and metabolites (calcium-gate, glucose channel) and enzymatic functions (phospholipases, adenylate cyclase). With regard to their degree of incorporation into the plasma membrane, proteins can be divided into two categories (Figure 22):

• The intrinsic (or integral) proteins are inserted in, and sometimes even extend through the membrane. They possess hydrophobic domains, which allow them to

Receptor Proteins Cell Membrane

Figure 22 Structure of the plasma membrane: Integral proteins are embedded in the lipid bilayer by hydrophobic interactions between the amino acid residues protruding from their alpha helices and the hydrophobic tailes of the lipids. (Nelson and Cox, 2000). Principles of Biochemistry by Albert L. Lehninger, et al. © 2000, 1993, 1982 by Worth Publishers. Used with permission.

Figure 22 Structure of the plasma membrane: Integral proteins are embedded in the lipid bilayer by hydrophobic interactions between the amino acid residues protruding from their alpha helices and the hydrophobic tailes of the lipids. (Nelson and Cox, 2000). Principles of Biochemistry by Albert L. Lehninger, et al. © 2000, 1993, 1982 by Worth Publishers. Used with permission.

Figure 23 Phospholipid movements in the membrane. Easy: rapid lateral diffusion within the plane of membrane, difficult: "flip-flop" from one face of the bilayer to the other.

Figure 23 Phospholipid movements in the membrane. Easy: rapid lateral diffusion within the plane of membrane, difficult: "flip-flop" from one face of the bilayer to the other.

'sink' into the hydrophobic core of the lipid bilayer. Proteins (such as cell surface receptors) which extend through the membrane have one or more hydrophobic regions of about 25 amino acids long that pass through the membrane (i.e. as an alpha helix, with the hydrophobic amino acid residues in contact with the hydro-phobic tails of the lipid molecules) and hydrophilic regions that are exposed to the water at the intra- and extracellular faces of the membrane.

• The extrinsic (or external) proteins are 'loosely' associated to membrane lipids and/or intrinsic proteins via ionic bonds, sometimes involving divalent cationic bridges.

In 1972, Singer and Nicholson proposed their 'fluid mosaic' model wherein both lipids and intrinsic proteins are allowed to diffuse freely within the plane of the membrane. However, both are not allowed to 'flip-flop' from one face of the membrane to the other (Figure 23). Whereas some proteins may form stable complexes, other can undergo dynamic interactions with each other.

During the past two decades, a considerable amount of information has been gathered about the structure of membrane-located receptors as well as about the molecular mechanisms by which they are able to transfer information across the cell membrane. These receptors are all intrinsic proteins which extend through the membrane. Their binding site for the chemical messengers is exposed at (or at least accessible from) the extracellular side of the plasma membrane. However, they are unable to translocate these messenger molecules across the membrane. Instead, they transfer 'information' (i.e. the presence of a bound messenger) across the membrane by undergoing a conformational change. This conformational change will alter certain pathways in the cell metabolism, and this will give rise to the 'cellular response'. These cell-surface receptors can be divided into three major classes according to the mechanism that they use for the transfer of information (Figure 24):

• (A) Direct control of membrane ion channel activity (receptor makes part of an ion channel).

• (B) Interaction with effector components (enzymes, ion channels) via mainly G proteins.

• (C) Direct control of enzymatic activity (i.e. the receptor possesses intrinsic tyrosine kinase activity or regulates the activity of an associated kinase).

Transfer Membrane
Figure 24 Major mechanisms for receptor-mediated transfer of information across the cell membrane.
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