Principles of Protein Structure - H. Schulz 1982

Covalent Protein Structure
Enzyme-Controlled Modifications of the Main Chain
N- and C-termini

To understand many aspects of Cell/13.html">Protein Structure Organization, it is essential to have a clear picture of its physiological journey throughout the entire cycle from synthesis to degradation. This is particularly important for Proteins that undergo post-translational (secondary) modifications, i.e., alterations in the covalent bonding system following their synthesis on the ribosome.

A classic example of how significantly proteins are modified and processed during and after synthesis is the biogenesis of Collagen [85, 125—131]. Apparently, it involves a greater number of reactions than shown in Fig. 4.4. It is clear, however, that The pathway of collagen is quite remarkable. The following sections describe some general aspects of protein modification in vivo.

N-terminal Amino groups are frequently modified. The N-terminal α-ammonium group (pK ~8) of many proteins undergoes secondary modification (see review [132]). It is acetylated in the tobacco mosaic virus coat protein, in most c-type Cytochromes, in Muscle Proteins, Actin, Myosin, Tropomyosin, parvalbumin, adenylate kinase, and Lactate dehydrogenase. Other Examples include wool keratin and α-melanocyte-stimulating hormone [132]. A similar Modification of the α-amino group—formylation—has been found in bee venom melittin and in lamprey Hemoglobin. A substantially different modification of the polypeptide N-terminus is The conversion of the N-terminal glutamic acid into a pyrrolidonecarbonyl group. Such a modification has been found in many extracellularly functioning proteins, such as the light and heavy chains of human IMMUNOGLOBULINS, Hormones isolated from various sources, and snake venoms [132—134].

The Biological Significance of α-amino group masking remains insufficiently clear; it may protect the protein from aminopeptidase attack or facilitate the anchoring of the N-terminal region of the polypeptide in a nonpolar environment, either on a receptor molecule or within the protein itself, thereby preventing its contact with the solvent. This hypothesis does not apply to the α-amino group methylation found in ribosomal proteins isolated from Escherichia coli [135], since methylation does not eliminate the charge. The Physiological Role of α-amino group Acetylation is perfectly clear in certain fish Hemoglobins: this modification helps maintain oxygen-binding capacity independently of ambient pH, thereby preventing the release of excess oxygen into the swim bladder [136] (Section 10.3).

C-terminal modifications are rare. For naturally occurring Polypeptides, the only known substituent at the C-terminus is the amide group. Amidated C-terminal groups have been found, in particular, in hormones and bee venoms [132]. The function of the amide group presumably involves protecting the peptide chain from carboxypeptidase attack or facilitating the accommodation of the negatively charged C-terminus (whose α-CO₂H group pK is around 3) in a nonpolar environment. As a rule, C-terminal modifications are significantly rarer than N-terminal ones.