They are made up of structurally folded polypeptide chains.
Globular proteins or hemoproteins are spherical (“globe-like”) proteins and are one of the standard protein types (the others are fibrous, messy, and membrane proteins).
Globular proteins are somewhat soluble in water (forming colloids in water), unlike fibrous or membrane proteins. There are multiple classes of round protein folds, as there are many different architectures that can fold into a more or less spherical shape.
The term globin can more specifically refer to proteins, including the globin fold.
Nature of proteins
Globular proteins are quite different from the ordinary molecules of organic chemistry.
The long polypeptide chain folds so that, in general, the hydrophobic side chains are predominantly on the inside, with the hydrophilic ones mostly outside, so the entire structure is held together by the pressure of hydrogen-bond water molecules external.
However, the careful packaging of specific groups within the protein is organized and maintained through numerous weak to medium electrostatic bonds (hydrogen and salt bonds).
Peripheral hydrophilic groups virtually dissolve in water, whose pH, ionic composition, etc., affects the delicate balance that maintains the native state of the protein.
In particular, the tendency of a protein to crystallize is easily altered by these solutes and by substances (such as polyethylene glycol and PEG) that change, even slightly, the properties of water.
Crystals can sometimes be grown if that equilibrium swings gently toward adhesion and allows enough time for these giant molecules to soften into a crystal lattice.
Once they are in that flexible federation, they are linked by a few weak intermolecular bonds between adjacent groups.
Most of its surface remains dissolved in the solvent that makes up at least a third of the volume of the protein crystal, which is a delicate object, easily broken when grasping and shrinking under the slightest dehydration.
However, many corresponding specimens for electron microscopy are not more robust, but this technique imposed, for many decades, much harsher conditions on them.
Whereas protein crystallography began with discovering appropriate sample presentation methods, electron “crystallography” only found them after decades of development.
Globular structure and solubility
Globular protein is quite old (probably dating back to the 19th century). It is now somewhat archaic given the hundreds of thousands of proteins and the more elegant and descriptive vocabulary of structural motifs.
The spherical nature of these proteins can be determined without the means of modern techniques but only by using ultracentrifuges or dynamic light scattering techniques.
The tertiary structure of the protein induces the spherical form. The apolar (hydrophobic) amino acids of the molecule are bounded towards the inside of the molecule. In contrast, the polar (hydrophilic) amino acids are bound outwards, allowing dipole-dipole interactions with the solvent, which explains the molecule’s solubility.
Globular proteins are only marginally stable because the free energy released when the protein folds into its native conformation is relatively tiny. This is because protein folding requires entropic cost.
As a primary sequence of a polypeptide chain, it can form numerous conformations; the native globular structure restricts its conformation to only a few. It decreases randomness, although non-covalent interactions, such as hydrophobic interactions, stabilize the system.
Although it is still unknown how proteins fold naturally, new evidence has helped advance understanding.
The problem with protein folding is that several weak non-covalent interactions are formed, such as hydrogen bonds and Van der Waals interactions.
Through various techniques, the protein folding mechanism is currently being studied. Even in the denatured state of the protein, it can be folded into the correct structure.
Globular proteins appear to have two mechanisms for protein folding, either the diffusion collision model or the nucleation condensation model. However, recent findings have shown that globular proteins, such as PDZ2 PTP-BL, fold with characteristic features. Of both models.
These new findings have shown that the transition states of proteins can affect the way they are withdrawn.
Globular protein folding has also recently been linked to the treatment of diseases. Anticancer ligands have been developed that bind to the folded protein but not the natural protein. These studies have shown that the folding of globular proteins affects their function.
According to the second law of thermodynamics, enthalpy and entropy changes contribute to the free energy difference between unfolded and folded states.
The free energy difference in a globular protein that results from folding into its native conformation is slight. It is marginally stable, thus providing a fast rotational speed and effective control of protein synthesis and degradation.
Unlike fibrous proteins that only have a structural function, globular proteins can act as:
- Enzymes catalyze organic reactions in the body under mild conditions and with excellent specificity. Different esterases fulfill this function.
- Messengers by transmitting messages to regulate biological processes. Hormones perform this function, that is, insulin, etc. Transporters of other molecules across membranes.
- Stocks of amino acids. Globular proteins, rather than fibrous proteins, also perform regulatory functions.
- Structural proteins, for example, actin and tubulin, are globular and soluble as monomers but polymerize to form long, stiff fibers.
Globular proteins tend to have a single specific conformational structure. The general topological and conformational characteristics of a protein are mainly governed by:
- Structural cross-links composed of covalently linked disulfide bonds and prosthetic groups, and non-covalent cross-links such as hydrogen bonds, hydrophobic interactions, and various forces.
- Continuous refolding to native conformations. Sometimes the addition of organic solvent alters the conformational flexibility and structure of a protein due to the change in the dielectric constant, leading to an overall change in the stability of the protein molecule under consideration.
The addition of reducing agents and materials like guanidine results in a reduction of the disulfide bonds responsible for maintaining the three-dimensional structures of proteins.
The reduction in disulfide bonds increases intrinsic viscosity, suggesting that globular proteins are unfolding to loosen, expanding randomly spiral chains. This process is called denaturation.
The definition of denaturation is the non-proteolytic modification in a structure of a natural/native protein, which produces a change in the sea in its physical, chemical, and, ultimately, biological activity.
Protein denaturation is confirmed and evaluated by techniques such as intrinsic viscosity determination, optical rotation differential ultraviolet spectroscopy, and others.