Polypeptide chain covalent bonding forces

About 200 to 460 kJ/mol are required to break a single covalent bond, whereas weak interactions can be disrupted by a mere 4 to 30 kJ/mol. Individual covalent bonds that contribute to the native conformations of proteins, such as disulfide bonds linking separate parts of a single polypeptide chain, are clearly much stronger than individual weak interactions. Yet, because they are so numerous, it is weak interactions that predominate as a stabilizing force in protein structure. In general, the protein conformation with the lowest free energy (that is, the most stable conformation) is the one with the maximum number of weak interactions. 

Larger proteins often contain more than one polypeptide chain. These multi-subunit proteins have a more complex shape, but are still formed from the same forces that twist and fold the local polypeptide. The unique three-dimensional interaction between different polypeptides in multi-subunit proteins is called the quaternary structure. Subunits may be held together by noncovalent contacts, such as hydrophobic or ionic interactions, or by covalent disulfide bonds formed from the cysteine residue of one polypeptide chain being cross-linked to a cysteine sulfhydryl of another chain (Fig. 15). 

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). 

In many of the haemoproteins we shall be discussing, the protoporphyrin IX group is held to the polypeptide chain only by hydrogen bonding, Van der Wools forces and iron-protein bonds. In several other cases, notably in cytochrome-c and its related compounds, the haem is covalently linked to the protein via substituents at the pyrrole carbon atoms. Cyto-chrome-c can be regarded as an iron protoporphyrin IX group with the addition of a protein cysteine side-chain across the vinyl double bonds giving two thio-ether links (Fig. 3). 

Val-Cys-Ser-Leu-Tyr-Gln-Leu-Glu-Asn-Tyr-Cys-Asn-COO-. When only the composition is known (i.e., the sequence is unknown), the amino acids are separated by commas and enclosed in parentheses, for example, (Ala,Cys2,Gly) means a peptide containing one Ala, two Cys, and one Gly in an unknown order. A "polypeptide chain" is, by convention, a continuous chain linked only by peptide bonds. A protein may have only one polypeptide chain and then the polypeptide and the protein are synonymous. In other cases, a protein may have more than one polypeptide chain, as does insulin. In such cases, the different peptide chains within a protein may be held together by noncovalent forces, as in the case of hemoglobin, sometimes supplemented by covalent cystine cross links, as in the case of insulin. In many cases, the noncovalent interactions allow more than one conformation and a protein may switch from one conformation to another as part of its function. 

Many types of forces and interactions play a role in holding a protein together in its correct, native conformation. Some of these forces are covalent, but many are not. The primary structure of a protein—the order of amino acids in the polypeptide chain—depends on the formation of peptide bonds, which are covalent. Higher-order levels of structure, such as the conformation of the backbone (secondary structure) and the positions of all the atoms in the protein (tertiary structure), depend on noncovalent interactions. If the protein consists of several subunits, the interaction of the subunits (quaternary structure. Section 4.5) also depends on noncovalent interactions. Noncovalent stabilizing forces contribute to the most stable structure for a given protein, the one with the lowest energy. 

It is our opinion that the pol)ipeptide chain structure of proteins, with hydrogen bonds and other interatomic forces (weaker than those corresponding to covalent bond formation) acting between polypeptide chains, parts of chains, and side-chains, is compatible not only with the chemical and physical properties of proteins but also with the detailed information about molecular structure in general which has been provided by the experimental and theoretical researches of the last decade. Some of the evidence substantiating this opinion is mentioned in Section 6 of this paper. 

Simple antibody molecules are Y-shaped (Fig. 2.48). Mainly they consist of four polypeptide chains, which are held together by covalent bonding and intermolecular forces. 

There are various levels of structural organization of proteins primary, secondary, tertiary and quaternary. The primary structure has been defined as the sequential order of amino acid residues linked by covalent peptide bonds. The secondary structure refers to the molecular geometry located in the polypeptide chains within ordered structures, such as a-helix, (3-sheet and random coil (unordered). The tertiary structure contains the information on how the elements of the secondary structure are folded. Finally, the quaternary structure of a protein with more than one polypeptide chain shows how the different principal chains are associated and oriented with one another. The structure of proteins is stabilized by different types of interactions covalent and hydrogen bonds, hydrophobic interactions, electrostatic and van der Waals forces [3,4]. 

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