Protein Structure II Highlights
1. Disruption of forces that stabilize protein structure cause folded proteins to unfold. Unfolded proteins are not functional. We describe them as denatured. Denaturing agents include heat, detergent, acid or base.
2. Fibrous proteins are proteins that have primary and secondary structure, but virtually no other higher order structures (tertiary or quaternary). They are essentially long fibers or shees of secondary structure. Examples include collagen, keratin (hair), or silk.
3. Myoglobin is a protein that acts like a ‘battery’, storing oxygen in muscles until it is needed. It is related to the oxygen transport protein called hemoglobin, but does not have a signicant function in transporting oxygen – only storing it.
4. Myoglobin contains a functional group called ‘heme’. Heme is composed of a ring called Protoporphyrin IX plus an iron atom. Heme is closely related to chlorophyll. Carbon monoxide and molecular oxygen can both bind to the iron of the heme group.
5. Hemoglobin differs from myoglobin in containing four polypeptide subunits instead of one. Interactions between multiple polypeptide subunits of a protein are called quaternary structure.
6. Hemoglobin contains two alpha and two beta subunits, each carrying one heme molecule. Binding of an oxygen molecule by one subunit causes a slight conformational change in the subunit and that causes a slight quaternary change that causes an adjacent subunit to bind oxygen with greater affinity. This is referred to as cooperativity. When hemoglobin is in the state of high affinity for oxygen (wants to bind oyxgen), we say it is in the R state. When it is in the low affinity state for oxygen (wants to release oxygen), we say it is in the T state.
7. Cooperativity requires multiple subunits. Myoglobin, which has only one subunit, does not exhibit cooperativity. Thus, myoglobin’s affinity for oxygen does not change as the oxygen concentration changes. This is not a good property for carrying oxygen, but is great for storing oxygen. It is for these reasons that myoglobin is used to store oxygen and hemoglobin is used to carry oxygen.
8. In the lungs, the oxygen concentration is high, so hemoglobin easily gets loaded up with oxygen. In tissues, where oxygen concentration is low, one of the oxygens comes off of hemoglobin and the reversal of what happened above occurs. Loss of one oxygen by hemoglobin favors loss of the others and oxygen is dumped where it is needed. There are other ways that oxygen is released from hemoglobin and they are related to the needs of rapidly metabolizing (respiring) cells for oxygen.
9. Adult hemoglobin contains a tiny pocket in the middle of it that can bind a molecule called BPG (also called 2,3BPG). BPG is produced by actively respiring tissues. When 2,3BPG is bound, hemoglobin loses some affinity for its oxygen (changes to T state) and lets it go. Hemoglobin drops 2,3BPG before it gets to the lungs and it is broken down readily, if you’re not a smoker. In smokers, however, 2,3BPG is in greater abundance in the blood, so hemoglobin has reduced oxygen carrying capacity, due to more of it coming to the lungs bound to 2,3 BPG and is thus locked in the T state.
10. The Bohr effect relates to the fact that hemoglobin loses affinity for (lets go of) oxygen the more acidic the environment in which the hemoglobin is found. Any tissue, such as muscles, when actively using energy, produces acid. Active tissues require more oxygen than non-active tissues, as we will see later in the course. Thus active tissues get more oxygen dumped on them by hemoglobin, due to the Bohr effect. The Bohr effect arises from binding protons to amine groups in hemoglobin, converting them from a charge of zero to a charge of plus one. This affects the protein’s structure and oxygen carrying properties.
11. Hemoglobin can also carry carbon dioxide. CO2 is a byproduct of actively respiring tissues. When hemoglobin picks up protons near active tissues, it dumps the oxygen and picks up CO2, which it transports it back to the lungs. In the lungs, the protons and CO2 come off. They are actually forced off due to the high oxygen concentration. When CO2 comes off, it is exhaled. Note that carbon dioxide is NOT carried by heme groups (unlike carbon monoxide and oxygen), but is intead carried elsewhere in the protein.
12. Fetal hemoglobin differs from adult hemoglobin in that the two beta subunits are replaced by two gamma subunits. This changes hemoglobin’s structure very slightly so that 2,3BPG can’t bind. Consequently, fetal hemoglobin spends more time in the R state and therefore has great oxygen affinity so it can take oxygen away from the adult hemoglobin of the mother.
13. Sickle cell anemia arises from a mutation in one of the hemoglobin subunits. This mutation causes hemoglobin to polymerize under low oxygen conditions and converts the blood cells into a sickle shape. They get stuck in capillaries when this happens. The condition can be life threatening, in some cases.