Ch. 6 Flashcards
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 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 do different types of molecules get across cell membranes?
How do you calculate free energy of transport?
How does porin passive transport work?
- Ion or small molecule is transported via porin passive transport protein
- Substrate carrier protein transports ion or small molecule through the periplasmic space
- Substrate carrier protein transports ion to coupled ABC active transport protein
What does a K+ ion channel do?
- Does not allow passage of Na+
- Diameter of Na+ is smaller than that of K+
- Selectivity filter of TVGYG sequence means Na+ is too small to interact with the amino acids which means dehydration cannot occur and it must be dehydrated to pass through small channel
- K+ channel directs K+ out of the intracellular space
What is the structure and function of aquaporins?
- Tetrameric protein complexes
- Transport water molecules across a hydrophobic membrane
