Principles of Biochemistry Volume 1 - A. Lehninger 1985

Biomolecules
Globular proteins: structure and function of hemoglobin
The polypeptide chains of globular proteins are folded into a dense, compact structure

В глобулярных белках полипептидная цепь свернута в компактную глобулу. Белки этого класса, значительно более сложные по Конформации, чем Фибриллярные белки, способны выполнять самые разнообразные биологические Функции, причем их активность носит не статический, а динамический характер. К глобулярным белкам относятся почти все из 2000 или даже большего числа известных ферментов. Некоторые Глобулярные белки выполняют транспортные функции: вместе с током крови они переносят кислород, Cell/8.html">Питательные вещества и неорганические ионы; к этому же классу белков принадлежат Антитела, ГОРМОНЫ, а также компоненты мембран и рибосом.

In this chapter, we will explore how the polypeptide chains of certain Globular Proteins fold in space and how their Amino Acid Sequence determines their three-dimensional Structure. We will also see that the native folded conformation of globular proteins is a necessary prerequisite for their biological activity. Next, we will examine the chemical and biological properties of Hemoglobin, the protein found in erythrocytes that serves as an oxygen carrier, and discuss related medical implications. Using Hemoglobin as an example, we will illustrate how the three-dimensional Introduction/12.html">Structure of Globular proteins is adapted to perform their vital biological Functions.

Two sets of data clearly demonstrate that the polypeptide chains of globular proteins are tightly folded and that this conformation is essential for these proteins to perform their biological functions. The first set of data concerns the Denaturation of native globular proteins occurring upon heating, exposure to extreme pH values, or Treatment with urea (Sec. 6.12). During denaturation, the covalent backbone STRUCTURE OF THE globular protein remains intact, but the polypeptide chain unfolds, assuming a disordered, irregular, and flexible spatial conformation. A denatured globular protein typically becomes insoluble in aqueous systems at a pH around 7 and generally loses its biological activity.

A second line of Evidence for the folded conformation of globular proteins comes from comparing the length of their polypeptide chains with the actual dimensions of their molecules, calculated from physicochemical measurements. For example, serum albumin (mol. mass 64 500) has a single polypeptide chain consisting of 584 amino acid residues. If this chain were in a fully extended ß-conformation, its length would be nearly 200 nm and its thickness about 0.5 nm. If it were folded into a continuous α-Helix, it would have a length of approximately 90 nm and a thickness of 1.1 nm (Fig. 8-1). However, physicochemical measurements show that the maximum dimension of a native serum albumin molecule is about 13 nm, and its diameter is approximately 3 nm (Fig. 8-1). Clearly, the polypeptide chain of serum albumin must be very tightly folded; otherwise, the molecule of this protein could not have the dimensions indicated above. It is now firmly established that all globular proteins are compactly folded in a specific manner, which gives rise to their biological activity. The folding pattern of the polypeptide chains of globular proteins into a compact spherical globule will be referred to as the tertiary structure.

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Fig. 8-1. Dimensions of the bovine serum albumin molecule in its native globular conformation. Serum albumin contains 584 residues in its single polypeptide chain. Shown on the left are the approximate dimensions this polypeptide chain would have if it were a continuous α-helix or entirely in an extended ß-conformation. The actual dimensions of the native serum albumin molecule are shown on the right.

Several obvious questions arise. How can the folding pattern of chains in globular proteins be determined? Is the folding of polypeptide chains the same in all globular proteins? What forces stabilize the chain in its folded conformation?