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CHMI 2227E Biochemistry I. Proteins: Quaternary structure. Quaternary structure. Quaternary structure involves several polypeptides: Oligomers Heteromers
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CHMI 2227EBiochemistry I Proteins: Quaternary structure CHMI 2227 - E.R. Gauthier, Ph.D.
Quaternary structure CHMI 2227 - E.R. Gauthier, Ph.D.
Quaternary structure involves several polypeptides: Oligomers Heteromers These subunits interact with each other through the usual weak interaction forces (H bonds, Van der Waals, ionic interactions, hydrophobic interactions) and/or though disulfide bonds; For aquous proteins, frequently, but not always, the interface between two subunits is made of hydrophobic amino acids. For membrane-bound proteins, the amino acids at the interface between the subunits are usually hydrophilic; hydrophobic hydrophilic Porin: a trimeric membrane-bound protein Quaternary structure CHMI 2227 - E.R. Gauthier, Ph.D.
Made up of 4 polypeptide chains: 2 copies of a-subunit (or HbA): yellow and blue; 2 copies of b-subunit (or HbB): red and pink Each subunit binds its own heme group: so each subunit can bind O2 Each subunit is highly similar in structure to myoglobin; Both hemoglobin and myoglobin bind O2 in a very similar fashion Quaternary structureHemoglobin CHMI 2227 - E.R. Gauthier, Ph.D.
HbA Myoglobin Quaternary structureHemoglobin HbA vs myoglobin CHMI 2227 - E.R. Gauthier, Ph.D.
4 major residues surround the heme group: Phe 43 His 64 Val 68 His 93 These amino acids create a hydrophobic environment while help hold the heme group in place; Also: His 93 binds the Fe2+ atom; Quaternary structureOxygen binding by Hb and myoglobin CHMI 2227 - E.R. Gauthier, Ph.D.
O2 binds the Fe2+ atom of the heme group, and is held in place with His 64; Oxygen-bound myoglobin/Hb is called oxymyoglobin/oxyHb Oxygen-free myoglobin/Hb is called deoxymyoglobin/deoxyHb Now, if both Myo and Hb can bind O2, why is it that Hb is a multimeric protein, while myoglobin is monomeric??? WHY???? Quaternary structureOxygen binding by Hb and myoHb CHMI 2227 - E.R. Gauthier, Ph.D.
O2 binding to myoglobin shows a simple equilibrium where the amount of O2 bound-myoglobin (y) directly depends on the concentration of O2 present; However, O2 binding to Hb is more complex: At low O2 concentration, very little Hb binds O2 even as the concentration of O2 increases (part A of the Hb curve); However, at a certain threshold of O2 concentration, Hb becomes rapidly saturated with O2 (part B of the Hb curve); B A Quaternary structureOxygen binding by Hb and myoHb CHMI 2227 - E.R. Gauthier, Ph.D.
At high O2 concentrations, both myoglobin and Hb are saturated, meaning there are no more O2-binding spots available. Interestingly: the affinity of myoglobin and Hb for oxygen varies by a factor of 10: Only 2.8 Torr are required to get 50% of myoglobin saturated; However, 26 Torr are required to half-saturate Hb. B A Quaternary structureOxygen binding by Hb and myoHb CHMI 2227 - E.R. Gauthier, Ph.D.
In the deoxyHb form, Fe2+ is bonded to 5 ligands: His 93 and 4 amines from the heme group; When one subunit of Hb binds O2, the Fe2+ atom moves foward the plane of the heme group, pulling with it the His 93 and the a-helix; This causes a slight but significant change in the tertiary structure of all the other Hb subunits, even if they are in the deoxyHb form; Quaternary structureO2 binding changes the 3-D shape of Hb CHMI 2227 - E.R. Gauthier, Ph.D.
The consequence of this slight change in conformation is an increase in the affinity of these other Hb subunits for O2; This phenomenon, where a change in the shape in one subunit trigger similar changes in other subunits of the same molecule, is called cooperativity; Molecules exhibiting cooperativity are also called allosteric molecules; Quaternary structureO2 binding changes the 3-D shape of Hb CHMI 2227 - E.R. Gauthier, Ph.D. http://upload.wikimedia.org/wikipedia/commons/0/07/Hb-animation2.gif
This phenomenon explains very well the behaviour of Hb in the presence of O2: At low pO2, all of the Hb subunits in the molecule are in the deoxy form with low affinity for O2: they bind O2 very poorly; At higher pO2, one of the 4 subunits binds O2, changes its conformation to the one with high affinity, and transmits this change in 3D structure to the other 3 subunits; The other 3 subunits, now having high affinity for O2, readily bind the molecule and rapidly become saturated. O2 O2 O2 O2 O2 O2 O2 O2 O2 O2 O2 O2 O2 O2 Low affinity High affinity Saturated Quaternary structureHb is an allosteric protein CHMI 2227 - E.R. Gauthier, Ph.D.
If Hb behaved like Myoglobin, then most of the Hb molecules would remained tightly bound to O2 and would not unload O2 in tissues; Conversely, if myoglobin behaved like Hb, it would readily let go of its O2, drastically limiting our muscles ability to perform aerobic work; Quaternary structureWhy Hb is allosteric, while Myoglobin is not? CHMI 2227 - E.R. Gauthier, Ph.D.
The Bohr effect concerns the observed decrease in O2 binding by hemoglobin when the pH is lowered; This effect explains why hemoglobin binds O2 in the lungs, and releases it in the tissues; The Bohr effect http://www.aw-bc.com/mathews/ch07/fi7p16.htm CHMI 2227 - E.R. Gauthier, Ph.D.
Gas exchangeIn the tissues Glucose + O2 CO2 H2O Carbonic anhydrase CO2 H2CO3 Hb-4O2 H2O + Cl- HCO3- HCO3- (to lungs) H+ ATP Hb-H+ 4O2 4O2 Plasma Erythrocytes Tissues CHMI 2227 - E.R. Gauthier, Ph.D.
Gas exchangeIn the lungs CO2 CO2 CO2 H2O Carbonic anhydrase H2CO3 Air Hb-4O2 H2O + Cl- HCO3- HCO3- H+ Hb-H+ 4O2 O2 O2 Plasma Erythrocytes Lungs CHMI 2227 - E.R. Gauthier, Ph.D.
