One of the basic properties of proteins
is the ability to bind things ... things such as DNA
, other proteins, cell
surfaces, etc ... The tendency for a protein to bind a particular substrate
is called the affinity
, (also known as the binding constant, the association constant KA, or its inverse, the dissociation constant KD)
. Describing the affinity for a single molecule binding a protein is reasonably straight forward, and can be ascertained using various techniques that determine the ratio of free and bound substrate.
However, many proteins can have multiple binding sites. If each of these binding sites works independently, then the affinity of one molecule is not affected by what else the protein may be binding to. In some cases, binding at one site does affect binding at another site. For example, the galactose repressor is a protein that sits on the DNA that codes for proteins that consume galactose. It binds to the DNA here so that the cell cant make galactose digesting proteins. However, the galactose repressor protein can also bind the galactose sugar itself. When it does, it undergoes a conformational change (an internal shape change) that makes it stick the sugar and fall off the DNA. This is called allostery. This system of sugar - protein - DNA interaction is called an operon. It is a way of regulating cell metabolism. When there is no galactose in the cell, the protein blocks galactose eating machinery, saving the cell from wasting energy by making this machinery. However, once galactose enters the cell, the block is removed and now the cell can harvest the galactose.
Allostery is fundamental to a lot of biochemical processes. It is basically the way a protein becomes a machine. Another example of allostery is hemoglobin. Hemoglobin binds O2 in the lungs and sticks very tightly to it. However, once it reaches parts of the body which are oxygen poor, it needs to let go of the oxygen. This is accomplished by an allosteric interaction between CO2 and O2. The CO2 dissolved in the blood makes carbonic acid. This acid causes a conformational change in hemoglobin, causing it to drop oxygen and take up carbon dioxide.
The origins of allostery can be seen directly by looking at atomic level structures of proteins (see X-ray crystallography). These high maginification structures show how the protein is in one shape when bound to one molecule and another shape when bound to a second. The shape change when sugar binds to galactose repressor changes the protein in such a way that it can no longer stick to the DNA.
There are other types of binding regulation. Some proteins have multiple substrates which bind at the same site. These substrates then compete for interaction with the protein. The one with the greater affinity wins. This is the mindset applied to drug design, where researchers try to develop mimics of a substrate that bind better than the natural one, knocking out the function of the protein. These engineered substrates are called inhibitors. If a narcotic binds a pain receptor better than the natural signals, the receptor can no longer react to pain signals, and the sensation is abated. Inhibitors can also function through allostery by stabilizing a non-active conformation of the protein, also preventing it from carrying out its function.
Other ways proteins regulate their function