Visualization Homework – Take II 10-05-2006

Lapelosa, Mauro

Schneider, Bill

Singh, Abhishek Good explanation

A Delgado, Roberto Basically why I want to project in this image is the mayor proximity between the hemoglobin hemoglobin residues (green-red). As you can see in most of the areas red is closer to green than purple (myoglobin). This tells us that probably there is a bigger attraction between the aa residues in hemoglobin. This property can be related to the hydrofobicity relations between these residues, and then promoting them to collapse with other hemoglobin monomers to form the tetramer.

B Delgado, Roberto The upper molecule represents two of the structures of the hemoglobin tetramer. As you can see by the electrostatic image there is no significant repulsions to disestablish the molecule. Therefore the residues that are close to each other in those regions are more compatible and this interactions help hemoglobin to for a tetramer. In the case of myoglobin & hemoglobin the interactions are not very favorable. As you can se in the electrostatic image there are too many repulsions between the regions that are suppose to overlap. That could be the same situation between the other myoglobin structures and that could be one of the reasons of why myoglobin stays as a monomer.

A Hua, Xia Hemoglobin (Chain D) Myoglobin

Hua, Xia B Myoglobin Hemoglobin Chain D Chain C

Chen, Yu-Jen Pro120 Myoglobin (shown in pink at right panel) has a proline residue at position 120 (shown as ball and stick), which twists a small helix inward to its core. This slight structural change may keep it away from another molecule and thus eliminate a potential hydrophobic interaction with another molecule (distance is idicated). However, hemoglobin (cyan) has the same small hydrophobic helix interacting with another molecule.

A Swaroopa Paratkar and Srinivas Annavarapu Interactions between deoxyhemoglobin subunits : Alpha1 beta1 Hydrophobic alpha Arg31 with beta Gln127 Hydrogen bonds alpha Asp126 with beta Tyr35 Alpha1 alpha2 Hydrogen bond alpha Asp126 with alpha Arg141 Hydrogen bond alpha Lys127 with alpha Arg141 Alpha1 beta2 Compare with interactions between myoglobin and hemoglobin chain C.

Hydrophobic: Arg31 alpha1 with Gln127 beta1 B Hemoglobin Chain C Hemoglobin Chain D Swaroopa Paratkar and Srinivas Annavarapu Good explanation Hydrogen bond: Asp126 alpha1 with Tyr35 beta1

Arg31 alpha1 with Ala127 beta1 C Hemoglobin Chain C Myoglobin Swaroopa Paratkar and Srinivas Annavarapu Asp126 alpha1 with Gly35 beta1

Abraham 1997, Journal of molecular biology D References: Hydropathic analysis of the non-covalent interactions between molecular subunits of structurally characterized hemoglobins Abraham 1997, Journal of molecular biology Site-directed mutations of human hemoglobin at residue 35ß: A residue at the intersection of the 1ß1, 1ß2, and 1 2 interfaces Kavanaugh 2001, Protein science Swaroopa Paratkar and Srinivas Annavarapu

Chain D Val 34D Cys 112D His 116D Myoglobin G Q S Mao, Lili A Val 34D

Chain A myoglobin Chain C Chain D Mao, Lili B Chain A myoglobin Chain C Chain D Myoglobin has an even electrostatic distribution, which cannot form the core as the subunits do in hemoglobin.

Hemoglobin and Myoglobin He, Xianglan Hemoglobin and Myoglobin Why Tetramer ? (This image shows the interface of Hemoglobin chain A with Chain B. Hydrophobic residues in both chain are depicted in red. Hydrophilic residues and those in between are in blue in Chain A, and in white in Chain B ). The subunits still have hydrophobic residues on the surface, this lead to hydrophobic interactions between the two chains. Also, there are four hydrogen bonds between these two subunits. Why Monomer? (The hydrophobic residues are depicted in red, and hydrophilic ones are in blue ) For the Myoglobin surface, there are some hydrophobic residues presents. But these residues are not able to form hydrophobic interaction with another subunit because of the steric hindrance posed by the hydrophobic residues around them. (images are created by Chimera using PDB files )

Fig1. The difference in hydrophobicity between the hemoglobin A Tao, Yuan 1 2 3 Tao, Yuan Fig1. The difference in hydrophobicity between the hemoglobin C & D chain interface (right) and myoglobin counterpart. (RED indicates hydrophobic and BLUE indicates hydrophilic).The ribbon highlighted with green solid lines shows the residues in the interface and their counterparts in the myoglobin. There are more hydrophobic residues at the interface in hemoglobin.

B Tao, Yuan Fig2. The collision of myoglobin C-terminus part into the hemoglobin A chain when myoglobin is superimposed on the D chain. The last four residues GFQG (shown in RED) of myoglobin (surface shown in gray solid) forms a spatial intrusion into the hemoglobin A chain. So myoglobin cannot form a tetramer as well as D chain can.

The surface difference between chain D of hemoglobin and Myoglobin Han, Hua

Yildirim, Evrim A The electrostatic difference between hemoglobin chain D and myoglobin on the interaction surface with other chains myoglobin Hemoglobin chain D

Yildirim, Evrim B Possible streric clash of C terminal of myoglobin with chain A of hemoglobin Blue: chain A, cyan: C-terminal of myoglobin green: myoglobin

Zheng, Guohui The question that we are concerned is why monomers of myoglobin don’t get together to form tetramer as hemoglobin by hydrophobic force. What I show here is the hydrophilic surface of hemoglobin (4HHB) and myoglobin (2MM1). We can see that the hydrophilic surface of myoglobin has a great percentage of its total surface while the tetramer has a great part of hydrophobic surface at the interfaces of its subunits, meaning that it is not easy to be push myoglobin together by hydrophobic forces.

Jung, Jongjin Chain D Chain D Chain A/C Binding interface for chain B Lys, Arg Glu, Asp hydrophobic  How does hemoglobin tetramer? - I think the monomer shape makes the tetramer symmetry possible - Chain A/C is same and Chain B/D is same. In addition all the chains are similar. Driving force for heterochain binding is hydrophobic interaction. In the figure, especially binding interface for chain B, most of residues looks hydrophobic and it is stabilized interchain salt bridge. ( yellow circle, right figure) Between homochain, there is no significant hydrophobic interaction. There is only one salt bridge ( orange circle , left figure). It will also stabilize forming tetramer, however, it is not be main force. Probably there will be one salt bridge and no hydrophobic interaction between chain B and D

Ertekin, Asli A Figure 1. The steric hinderance in Myeglobin tetramer. Myeglobin shown in magenda and rest of the complex is shown in gray

Ertekin, Asli B Figure 2. The charged groups in the proposed myoglobin tetramer. The positive charged residues (red) in myoglobin (green) are found in positively charged environment formed by the complex (grey).

Shivani Goel Hemoglobin (grey) aligned with Myoglobin (purple) Surface in contact with the other chains Chain D Showing the Surface in contact with the other chains Hemoglobin has lesser hydrophilic amino acids on the surface in contact with other chains (shown in blue) in comparison to Myoglobin Hemoglobin (Chain D) Myoglobin Blue – Hydrophilic amino acids

Mb Hb-C No hydrophobic interaction Hb-D Hb-C Hb-D Hb-C Hydrophobic interaction Color scheme in bottom pannels: Green=hydrophobic; yellow=others

Hb-A Hb-A Hb-D Mb No steric clashes Steric clashes