Hemoglobin hydrophobic interactions

Imately 65 X 55 X 50 It Is composed of four polypeptide chains each resembling quite closely the myoglobin chain The three dimensional structure of the subunits Is held together by weak noncovalent bonds The polar amino acid side chains are In contact with the solvent, and the nonpolar residues are located In the Interior of the molecule or In regions which form the contacts between chains The heme group Is located In a pocket In each chain residues In contact with heme are Invariable ( e are the same In different mammalian hemoglobins) and the bonds between heme and chain are hydrophobic Interactions Contacts between like chains (a-a are... 

The quaternary structure of hemoglobin features strong interactions between unlike subunits. The i/3i interface (and its a2 2 counterpart) involves more than 30 residues, and its interaction is sufficiently strong that although mild treatment of hemoglobin with urea tends to cause the tetramer to disassemble into a/3 dimers, these dimers remain intact. The a (and a2/3i) interface involves 19 residues (Fig. 5-8). Hydrophobic interactions predominate at the interfaces, but there are also many hydrogen bonds and a few ion pairs (sometimes referred to as salt bridges), whose importance is discussed below. 

Many proteins consist of a single polypeptide chain, and are defined as monomeric proteins. However, others may consist of two or more polypeptide chains that may be structurally identical or totally unrelated. The arrangement of these polypeptide subunits is called the quaternary structure of the protein. [Note If there are two subunits, the protein is called dimeric , if three subunits trimeric , and, if several subunits, multimeric. ] Subunits are held together by noncovalent interactions (for example, hydrogen bonds, ionic bonds, and hydrophobic interactions). Subunits may either function independently of each other, or may work cooperatively, as in hemoglobin, in which the binding of oxygen to... 

Various types of proteins have been purified using hydrophobic interaction chromatography including alkaline phophatase, estrogen receptors, isolectins, strepavidin, calmodulin, epoxide hydrolase, proteoglycans, hemoglobins, and snake venom toxins (46). In the case of cobra venom toxins, the order of elution of the six cardiotoxins supports the hypothesis that the mechanism of action is related to hydrophobic interactions with the phospholipids in the membrane. 

Proteins containing more than one polypeptide chain, such as hemoglobin (see Topic B4), exhibit a fourth level of protein structure called quaternary structure (Fig. 8). This level of structure refers to the spatial arrangement of the polypeptide subunits and the nature of the interactions between them. These interactions may be covalent links (e.g. disulfide bonds) or noncovalent interactions (electrostatic forces, hydrogen bonding, hydrophobic interactions). 

If hydrophobic interactions are involved in this association, as has been suggested by Eauzmann (1959) on the basis of this observation, it should be sensitive to the introduction of small amounts of the appropriate weakly protic nonaqueous solvents. The endothermic association of sickle cell anemia hemoglobin (Murayama, 1956) is another case to investigate. 

Following the original work by Kauzmann on hydrophobic interactions and the determinations of the structures of myoglobin and hemoglobin, it was stated, and is still stated frequently (despite evidence to the contrary), that hydrophobic residues are buried in the interior of proteins and hydrophilic residues are exposed to solvent water. It was first shown by Klotz (1970 see also Lee and Richards, 1971) that a substantial proportion of the exposed solvent-accessible surface area of proteins is composed of nonpolar groups. This matter has been stressed in lectures for many years by one of the authors (H. McK.) (for a discussion of various approaches to this problem, see Edsall and McKenzie, 1983). In the case of lysozyme, a substantial proportion of the hydrophobic residues Leu, Val, He, Ala, Gly, Phe, Tyr, Trp, Met, and Pro are either fully exposed to solvent or at least have some atoms that are solvent accessible. Examples of hydrophobic residues that are surface exposed are Val-2, Phe-3, Leu-17, Phe-34, Leu-75, Trp-123, Pro-70, and Pro-79, with Trp-62, Trp-63, Ile-98, Trp-108, and Val-109 being on the surface of the cleft. Examples of the least-exposed ionizable side chains are Asp-66, Asp-52, Tyr-53, His-15, and Glu-35. 

In hemoglobin, four similar units are connected in a tetramer by hydrophobic interactions. Binding of the first oxygen atom enhances the binding constants of the three remaining units. For such cooperative ( allosteric ) effects, which are typical for biological but out of reach for synkinetic systems, the reader is referred to biochemistry textbooks (Dickerson and Geis, 1969,1983 Voets, 1990). 

Coitformartonal slates of hemoglobin. In deoxyHb, the 4 subunits are relatively tightly associated, and the chains are linked by several noncovalent (ionic) bonds, as well as hydrophobic interactions. DeoxyHb is therefore known as the T-form (taut, tight or tense). The more important ionic bonds (salt bridges) of the T-form are free terminal NH2 of Val-1 (02) with the free (terminal) COOH of Arg-141, similarly Val-1 (oi) with Arg-141 (tij) guanidinium of Arg-141 (oi) with side chain COOH of Asp-126 (02), similarly Arg-141 (02) Asp-126 (o,) free (terminal)... 

Association and dissociation of protein molecules on hydrophobic surfaces may also take place. Small proteins comprised of a single pol) eptide chain, such as lysozyme, associate to form dimers upon adsorption on hydrophobic surfaces, especially near the pi of 11. Proteins that have a quaternary structure, such as hemoglobin, can dissociate into subunits upon contacting a hydrophobic surface, as the subunits are held together by hydrophobic interactions. 

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