Protein quaternary stmcture

In some proteins, such as hemoglobin, separate polypeptide chains must associate for the chains to be functional. This forms a quaternary stmcture. 

The diversity in primary, secondary, tertiary, and quaternary stmctures of proteins means that few generalisations can be made concerning their chemical properties. Some fulfil stmctural roles, such as the collagens (found in bone) and keratin (found in claws and beaks), and are insoluble in all solvents. Others, such as albumins or globulins of plasma, are very soluble in water. Still others, which form part of membranes of cells, are partly hydrophilic ( water-loving , hence water-soluble) and partly lipophilic ( lipid-loving , hence fat-soluble). 

Biochemically there are four major classifications of protein structure primary (amino acid sequence), secondary (local spatial arrangement), tertiary (overall 3D structure) and quaternary (protein complex stmcture). (Figure 1.8)... 

Many proteins exist in subunits of a composite structure. The organization of these subunits is termed the quaternary stmcture and is particularly important in enzyme-mediated reactions. The tertiary and quaternary structure of native protein in water can be distributed by addition of electrolytes, alkali solutions, urea, or detergents and increasing temperatore. The properties change markedly for example enzyme activity is often lost. In most cases this denaturation is not reversible. 

The subunits are held together by the same kinds of interactions that hold the individual protein chains in a particular three-dimensional conformation hydrophobic interactions, hydrogen bonding, and electrostatic attractions. The quaternary stmcture of a protein describes the way the subunits are arranged in space. Some of the possible arrangements of the six subunits of a hexamer are shown here ... 

Proteins associate with each other to form quaternary structures. Many proteins consist of more than one subunit. For example, hemoglobin has a molecular weight of 64,000 and is composed of four subunits, each of molecular weight 16,000. Two of the subunits are alike, and two are different. The enzyme tryptophan synthetase from Escherichia coli, which catalyzes the final two steps in the biosynthesis of that amino acid, consists of two nonidentical subunits, each of which catalyzes one reaction. Other enzymes contain regulatory and catalytic subunits. Still other enzymes consist of aggregates of two, three, or more identical subunits. The specific, noncovalent association of protein subunits is termed the quaternary stmcture of a protein. If the subunits are not identical, the association is called heterotypic. The association of identical subunits is termed homotypic. 

One of the most remarkable properties of self-assembly is its ability to generate exceedingly coinplica ted supramolecular structures from fairly simple components. Perhaps the most elegant embodiment of this phenomenon is protein stmcture. Proteins exhibit at least four hierarchies of stmcture primary, secondary, tertiary, and quaternary stmctures. Primary stmcture describes the covalent connections making up the sequence of amino acids in each strand. Secondary stmcture involves local architectural elements created when portions of a strand... 

Protein stmcture can be classified in a hierarchical fashion (Figure 1). The first level is the amino acid sequence or primary stmcture, and the next is the secondary stmcture, which is the regular repetition of backbone dihedral angles in a linear stretch of amino acids that gives rise to a common stmctural unit. The two dominant types of secondary structure in proteins are -helices and -sheets. Elements of secondary structure are connected by loops or turns, which allow them to fold back on themselves and to associate to form a globular tertiary stmcture. In some proteins the folded tertiary stmcture of a monomer is the active form, whereas in others monomers associate with other similar or dissimilar subunits to give specific higher-order complexes or quaternary stmcture. ... 

The tertiary stmcture of a protein is the complete three-dimensional stmcture of the polypeptide chain. If multiple polypeptide chains are present, the arrangement of their polypeptide chains with respect to each other is the quaternary stmcture in such cases, enzymes are polymers conposed of two or more subunits (Table 3). In order to illustrate the tertiary stmcmre of a protein, the three-dimensional stmcture of the glycolytic enzyme hexokinase is shown in Fig. 3 with the aid of a space-filling model. Hexokinase catalyzes the phosphorylation of D-glucose with ATP. The groove in the middle of the stmcmre is where the substrates bind (Cantor Schimmel, 1980). 

The more complicated design of tertiary and quaternary stmcture in proteins has been attained in some cases. However, the ability to form hierarchically ordered stmctures, or self-assemble folded stmctural units into well-defined higher order assemblies, from any non-natural backbone remains an important unsolved problem. A few preliminary reports, including work on p-peptides and peptoids, with stmcture beyond the helix were reported recently [20-22]. These two backbones represent the more weU studied sequences of foldamers and so initial reports toward stmctures beyond secondary elements can be expected. However, given more than a decade of foldamer research, little work toward these higher order stmctures has been reported. 

A quaternary stmcture is the arrangement of two or more protein subunits into a complex. These subunits may be identical but may also differ from each other. Interactions between subunits determine the three-dimensional orientation towards each other and therewith the structure of the whole protein (dimer, trimer, tetramer). The three-dimensional structure of proteins is essential for their biological efficacy and is highly sensitive to degradation. The chemical bonds in proteins can be disrupted by ... 

Explain what is meant by the quaternary stmcture of proteins. (Section 19.9)... 

Proteins have primary, secondary, tertiary, and quaternary stmcture.The primary structure of a peptide can be determined by using a combination of enzymes and small molecule reagents. There are several analytical tools that can also be applied to this task. Peptides can be synthesized by employing protecting groups and activating reagents. The common procedures are amide formation vdth tBoc or Cbz for amine protection, esterification with ethanol for carboxylic acid protection, and acid activation with DCC. 

Proteins are a-amino acids assembled into long polymeric chains. The secondary stmcture of these peptides or proteins involves the regions of a-helical or 3-pleated sheet arrangements, which are separated from each other by disordered sections of the chains called random coils. Disulfide bonds, electrostatic forces, van der Waals forces, and hydrogen bonding twist these molecules into shapes characteristic of individual proteins, the tertiary structure. Secondary and tertiary stmcture can be destroyed, sometimes only temporarily, by any of a number of denaturing processes. Finally, intermolecular forces can hold a number of these protein chains together to form supermolecules, the quaternary stmcture. 

These higher ordered structures are affected by the identities of the R groups on the constituent amino acids. It is the electronic and steric properties of the R groups that generate the particular secondary, tertiary, and quaternary stmctures of proteins. 

Not all proteins contain more than one subimit, so not all have a quaternary stmcture. Example Hemoglobin (see Fig. 20.21 in the text) contains four pol5q)eptide units and has a quaternary stmcture. 

It is true that the unambiguous elucidation of chiral recognition mechanisms on various protein-based CSPs is challenging and often difficult since precise information about the tertiary and quaternary stmctures of proteins is not always available. Multiple stereo-specific sites may be involved in chiral recognition process. However, it is encouraging to see the progresses that have been made in this field in recent years [17, 95—102]. 

Quaternary stmcture refers to the shape resulting from the assembly of two or more proteins, called subunits, to form a larger protein complex. In the case of hemoglobin, four subunits [two a subunits (purple), each consisting of 141 amino acids and two /3 subunits (pink), each consisting of 146 amino acids] make up the larger complex. 

Identifying the Primary, Secondary, Tertiary, and Quaternary Stmctures of Proteins (16.3, 16.4)... 

Figure C3.1.7. Time-resolved optical absorjDtion data for the Soret band of photo lysed haemoglobin-CO showing six first-order (or pseudo-first-order) relaxation phases, I-VI, on a logaritlimic time scale extending from nanoseconds to seconds. Relaxations correspond to geminate and diffusive CO rebinding and to intramolecular relaxations of tertiary and quaternary protein stmcture. (From Goldbeck R A, Paquette S J, Bjorling S C and Kliger D S 1996 Biochemistry 35 8628-39.)...

A schematic comparison of the levels of protein stmcture. Primary stmcture is the covalently bonded stmcture, including the amino acid sequence and any disulfide bridges. Secondary structure refers to the areas of a helix, pleated sheet, or random coil. Tertiary stmcture refers to the overall conformation of the molecule. Quaternary structure refers to the association of two or more peptide chains in the active protein. 

The primary structure of a protein is the order in which the individual amino acids are sequenced. This tells us little about the shape that the protein will assume in solution, although the primary stmcture naturally determines the secondary, tertiary and even quaternary forms. These amino acid building blocks (Table 11.2) give the key to stmcture and behaviour. The standard three-letter (Glu, Arg, Trp, etc.) and one-letter (E, R, W, etc.) abbreviations for amino acids are also listed their use makes stmctural descriptions more accessible. 

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