Structural Biochemistry/Enzyme Catalytic Mechanism/Membrane Protein

Biological membranes have phospholipid bilayer structure which contains a set of proteins which help plasma membrane to carry its distinctive functions. Membrane proteins can be attached to the membrane or associated with the membrane of a cell or an organelle. Membrane proteins can be classified into two groups based on the strength of their association with the membrane:

1. Integral membrane proteins(also called intrinsic proteins)have one or more segments that are permanently embedded within the phospholipid bilayer and have their domains on both sides of the membrane. Most integral proteins contain residues with hydrophobic side chains that interact with fatty acyl groups of the membrane phospholipids, thus anchoring the protein to the membrane. Most integral proteins span the entire phospholipid bilayer.It interacts extensively with the hydrocarbon chain of membrane lipid and they can be released by agents that compete for these nonpolar interaction.

2. Peripheral membrane proteins or extrinsic proteins are temporarily bound either to the lipid bilayer or to integral proteins by hydrophobic, electrostatic, and other non-covalent interactions. This type of proteins does not interact with the hydrophobic core of the phospholipid bilayer. They are usually bound to membrane by interactions with integral membrane proteins or directly by interactions with lipid polar head groups. This polar interaction can be disrupted by the change in pH.



Some membrane proteins are found bounded to lipid bilayer and generally involved in cell-cell signaling or interactions. Others are embedded within the lipid bilayer of a cell often form channels and pores. Membrane proteins can be attached to both the outside and inside of the cell membrane.

Proteins can be attached to the cell membrane in a variety of ways. One method involves irreversible covalent modification. Both Ras (a GTPase) and Src (protein tyrosine kinase) are known to be modified in this manner. Both of these proteins participate in signal transduction pathways, but upon covalent attachment of a lipid group they become attached to the inner face of the cytoplasmic membrane. When Ras and Src are affixed to the cell membrane they are better able to receive and transmit information being transferred via their respective signal transduction pathways.Membrane proteins can be made of alpha helices or beta strands,or the combination of both alpha helices or beta strands. For example the channel protein called Porin is made up of entirely beta strands, while the enzyme protein called prostaglandin is made entirely of the alpha helices.

Membrane proteins can be alpha - helices or beta - strands. Proteins can span the membrane with alpha helices. Membrane - spanning alpha - helices are the most common structural motif in membrane proteins. An examination of the primary structure reveals that most amino acids in the membrane protein are nonpolar and very few are charged. One of the first alpha - proteins found was the bacteriorhodopsin. It uses light energy to transport protons from inside the cell to outside generating a proton gradient used to form ATP. The seven alpha - helices are closely packed and arranged perpendicular to the plane of the cell and they span 45A in width. Membrane proteins can also be made out of beta strands. Beta Strands form channel proteins. They are less common than alpha - helices. Channel proteins are formed by beta arrangement of beta strands. Each strand is hydrogen bonded to its neighbor in an anti-parallel arrangement, forming a single beta sheet. The beta sheet then curls up to form a hollow cylinder that forms a channel in the membrane. An example is Porin. The outside surface is non-polar and interacts with the hydrocarbon core of the membrane, while the inside channel is hydrophilic and filled with water. The arrangement of polar and non-polar is accomplished by the alternation of hydrophobic and hydrophilic amino acids along with each beta strand.

Mutations in both Ras and Src have been observed in a number of cancer cells; it is thought that these mutations and the subsequent interruption of the signal transduction pathways predispose a cell to uncontrolled replication. When the presence of a mutation is detected a small protein named ubiquitin is attached to the damaged protein; this modification signals that the marked protein is to be destroyed. It is essential that the protein be destroyed before anaphase so that the damaged DNA is not passed on to other cells. The attachment of ubiquitin to a damaged protein is the first step of apoptosis, which is programmed cell death.

Fluidity of Membrane proteins
Biological membrane are flexible. This flexibility is attained by the fluidity of the protein. The fluid mosaic model allows lateral movements called the lateral diffusion, and sometimes the transverse diffusion or flip flop can occur, which takes longer time to take place.

Lateral diffusion Lateral diffusion is the movement of the lipid laterally which is very rapid, unless there is restriction by special interaction.



Flip-flop or Transverse diffusion

The condition is when transition of a molecule from one membrane surface to the other occurred. It is a very slow space compared with the lateral diffusion.It happens once in several hours.



Transverse Diffusion ( Flip-flop)