Fundamentals of Molecular Biology. Part 1: Molecular Biology of the Cell - A. N. Ogurtsov 2011

Molecular Principles of Protein Function
Protein Domains

The Tertiary Structure of Proteins with a molecular weight (MW) greater than 15,000 MW is usually subdivided into domains.

(Molecular weight, MW (molecular weight, MW) is measured in daltons, Da; 1 Da = 1 amu = 1.66-10 ²⁷ kg; 15,000 MW = 15 kDa).

Structurally, a domain is a compactly folded region of a polypeptide. Domains of large proteins can be determined using X-ray crystallography or Electron Cell/15.html">Microscopy.

Although domains are fairly well physically segregated from one another, they are nevertheless connected by interpenetrating segments of the polypeptide chain. For example, each of the subunits of the hemagglutinin protein contains a globular and a fibrillar domain (Figure 116(a)).

A structural domain consists of 100-150 residues. Often, a domain is characterized by some specific structural feature:

✵ an unusually high amount of a specific amino acid (e.g., Proline-rich domains or acidic domains),

✵ Amino acid sequences that repeat across many proteins,

✵ specific Secondary structure motifs (repeats) (e.g., a zinc finger).

Sometimes domains are defined not by their structural isolation, but by their Functions based on identifying the region of the protein chain that provides the protein's functional Specificity.

For instance, a specific region (or regions) provides catalytic activity (e.g., a kinase domain) or specific binding capability (e.g., a DNA-binding domain or a membrane-binding domain).

Functional domains are often identified experimentally by shortening the protein using proteases (Enzymes that cleave the peptide backbone) down to its smallest active fragment. Alternatively, Mutations are induced in the DNA encoding the protein in order to delete or alter Regions of the protein chain. The activity of such a "truncated" or modified protein synthesized from the mutant Gene is then analyzed, thereby determining which region of the protein dictates its functionality.

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Figure 116 - Domains: a - tertiary two-domain STRUCTURE OF THE hemagglutinin subunit; b - Quaternary Structure of hemagglutinin consisting of three subunits

The domain Organization of large protein molecules illustrates the principle by which complex molecules are formed from simpler components. Just as identical secondary structure motifs (repeats) are present in different proteins, tertiary structure domains can also be part of complex molecules across various proteins.

The modular principle of protein architecture is relatively easy to identify in large proteins, which essentially represent a mosaic assembled from various domains and, therefore, enable the simultaneous execution of multiple functions.

An example of such a module present in several proteins is the epidermal growth factor (EGF) domain (Figure 117).

Figure 117 - Scheme of the modular structure of various proteins

EGF is a small soluble protein hormone that binds to Cells during the embryonic phase of development, or to Skin and Connective Tissue cells in the adult Organism, triggering their division.

EGF is formed As a result of repeated proteolytic Cleavage of the EGF precursor protein, which is anchored in The Cell membrane by a transmembrane domain. EGF modules are also present in other proteins, for example, in (1) tissue plasminogen activator (TPA) - a protease used to dissolve Blood clots in patients with myocardial infarction, (2) the Neu protein, which is involved in embryonic Cell Differentiation, and (3) the Notch protein, which is part of the cell's membrane signaling system.

In addition to EGF domains, these proteins contain domains characteristic of other proteins as well. For example, TPA contains a Trypsin domain characteristic of all enzymes that facilitate protein degradation.