What are the 5 major functional classes of proteins?
- Metabolic enzymes
- Structural proteins
- Transport proteins
- Cell signaling proteins
- Genomic caretaker proteins
What is myoglobin?
A globular transport protein that is concentrated in muscle tissue and functions in oxygen storage
What is hemoglobin?
A tetrameric globular transport protein that transports oxygen from the lungs to the tissues through the circulatory system
What is heme?
Fe2⁺ porphyrin complex that functions as a prosthetic group, reversibly binding oxygen
What is the structure of myoglobin vs hemoglobin?
- Myoglobin: single polypeptide chain with one heme group
- Hemoglobin: 4 polypeptides with 2 alpha and 2 beta subunits
What residues are critical to heme binding?
2 histidine residues (proximal and distal)
What does heme binding do?
- Oxygenation of myoglobin and hemoglobin is bound through the sixth coordination bond
- Without oxygen, the heme is no longer planar because the ion is too large, resulting in a pucker –> deoxyhemoglobin
What is the T state (tense) conformation of hemoglobin?
- Conformation of hemoglobin in the absence of oxygen
- Deoxyhemoglobin
What is the R state (relaxed) conformation of hemoglobin?
- Conformation of hemoglobin when oxygen is bound
- Oxyhemoglobin
How do hemoglobin shift from T –> R?
- H bond forms between Tyr42 in the α1 subunit and Asp99 in the β2 subunit
- Upon oxygen binding, the two helices slide past each other, and a new hydrogen bond forms between Asp94 of the α1 subunit and Asn102 of the β2 subunit in the R state
What is fractional saturation?
The fraction of protein binding sites that are occupied
Draw the oxygen binding curves for myoglobin and hemoglobin.
What does a sigmoidal curve indicate?
Cooperative binding/cooperativity
What is cooperative binding/cooperativity?
When the binding of a molecule o a macromolecule lowers the energy of binding of subsequent molecules to that macromolecule
What are the 3 key features of ligand-protein interactions?
- Ligand binding is a reversible process involving noncovalent interactions
- Ligand binding induces or stabilizes structural conformations in target proteins
- The equilibrium between ligand-bound protein and ligand-free protein can be altered by the binding of effector molecules (induce conformational changes in the protein that increase or decrease ligand affinity)
What is the Bohr effect?
Oxygen binding in Hb depends on pH and [CO2]
What is the function of 2,3-bisphosphoglycerate?
- Traps hemoglobin in the T state and acts as a negative effector
- Facilitates O2 transport from maternal cells to fetal cells by its differential binding to α2β2 versus α2γ2
What is the structure of 2,3-BPG?
What is the function of allosteric regulation of hemoglobin?
Delivering O2 from the lungs to the tissues
What is the difference between fetal hemoglobin and adult hemoglobin?
- Fetal hemoglobin consists of a tetramer complex in which the normal adult β subunit is replaced by a special fetal hemoglobin subunit called γ
- His143 is replaced by Ser143 (eliminates 2 of the 6 positive charges in the 2,3-BPG binding site)
- TL;DR - fetal Hb has a different subunit that doesn’t bind 2,3-BPG, so fetal Hb can transport more oxygen
Compare maternal Hb, fetal Hb, and myoglobin.
What is sickle cell anemia?
- Recessive genetic disease involving substitution of valine for glutamate in a Hb polypeptide, leading to anemia
- RBC have sickle shape
How does sickle cell anemia result in malaria resistance?
- Even just carriers of the gene have shown more malaria resistance than people with normal Hb
- Deformed RBCs are removed by spleen, which removes infected cells from circulation
What are the 3 major types of membrane proteins in cells?
- Membrane receptor proteins
- Involved in transduction of a signal across the plasma membrane - Membrane-bound metabolic enzymes
- Membrane proteins embedded in the inner mitochondrial membrane (similar to chloroplast thylakoid membrane) - Membrane transport proteins
- Facilitate movement of polar molecules across the hydrophobic membrane
