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Haemoglobin structure and stability
A selection of talks on Biochemistry
The ERK1/2 MAPK cascade
- Prof. Melanie H. Cobb
- University of Texas Southwestern Medical Center at Dallas, USA
Amino acid conjugation: mechanism and enzymology
- Dr. Kathleen Knights
- Flinders University, Australia
Hello, and welcome to this Principles of Biochemistry lecture series. My name is Jerry Feigenson, I am a professor in the Department of Molecular Biology and Genetics at Cornell University in the USA. In the sixth lecture, you saw that proteins are thermodynamically stable, but most are not very stable. All information for the folding pattern is contained in the amino acid sequence. However, it is not at all clear how proteins can possibly fold up as fast as they actually do. Many proteins tend to misfold and therefore need some help. Proteins exhibit various types of motions.
In this lesson, you will learn that haemoglobin shows a sigmoid curve of oxygen binding. That haemoglobin has two different stable quaternary structures called the T- state and an R-state. The general principle of protein quaternary structure being tensed or relaxed was first discovered for haemoglobin. The haemoglobin T-state is stabilized by many pH-dependent ion pairs.
What's the role of the haem group? Well, you previously saw that the myoglobin protein is shaped to fit the haem group and hold it in a crevice. But here, let's consider what would be the ideal properties of a molecule designed to pick up oxygen in the lungs and then deliver oxygen to the tissue. We can make a graph of the fraction of haem groups that have an oxygen bound, and we call that fraction theta. We will graph theta against the oxygen pressure. Really, we should graph theta against the oxygen concentration, but that's hard to measure. So we measure oxygen pressure. So we'll make this plot for myoglobin. We see that there's a pressure of oxygen in the lungs and there's a much lower pressure in oxygen starved tissue. For myoglobin, at the oxygen pressure in the lungs, myoglobin is saturated with oxygen, so it meets that criterion of a molecule designed to pick up the oxygen. But there's another criterion, and that is, the molecule must give up the oxygen to where it is needed - oxygen starved tissue. Myoglobin does not do that. Myoglobin is still holding its oxygen in oxygen-starved tissue. So myoglobin is far from ideal as a molecule to pick up oxygen and then drop off oxygen. Now let's look at haemoglobin. So haemoglobin has a different shape of oxygen binding curve. It drops off a considerable fraction of its oxygen when it reaches oxygen starved tissue. We call this shape of the oxygen binding curve sigmoid or S-shape. But we use the term sigmoid.