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5.9:

Conjugated Proteins

JoVE Core
Cell Biology
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JoVE Core Cell Biology
Conjugated Proteins

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Proteins form complexes with other small and large molecules, including nucleic acids, carbohydrates, and lipids. These are called conjugated proteins, meaning their complexes consist of both amino acids and nonprotein components.

Nucleoproteins are comprised of both proteins and nucleic acids. 

Deoxyribonucleoproteins or DNPs contain DNA and are commonly found in the nucleus. In eukaryotic cells, DNA is tightly wrapped around histone proteins, forming nucleosomes, a crucial part of chromosome structure.

Ribonucleoproteins or RNPs contain RNA and can be located in the nucleus, as well as the cytoplasm. The spliceosome is a large complex of five small nuclear RNPs, or snRNPs containing both RNA and protein along with accessory cofactors. The spliceosome removes undesired nucleotides from a precursor gene transcript. 

Glycoproteins and proteoglycans are protein complexes that contain carbohydrates of varying sizes.

Antibodies are glycoproteins with short carbohydrate chains, critical for normal immune function. 

In contrast, proteoglycans are formed from long repeating sugar units.  Often these are modified sugars that contain other functional groups instead of a hydroxyl group. Proteoglycans are a major component of the extracellular matrix in long-bone cartilage, ensuring frictionless motion of the joints.

Lipids also combine with proteins to perform a variety of functions. 

Lipoproteins are water-soluble complexes, having a hydrophobic lipid core and hydrophilic protein surface. Insoluble cholesterol cannot travel freely through blood, so it binds to lipoprotein core, which aids in its transport. 

In contrast, proteolipids are water-insoluble complexes with hydrophobic amino acid residues attached to lipid molecules. Proteolipids are abundant in brain tissues where they can form an insulating coating that maintains normal motor functions.

Additionally, proteins form complexes with many other types of molecules.

Red blood cells derive their color from heme, a nonprotein component of hemoglobin. Heme has a central iron atom that binds and transports oxygen through the bloodstream.

5.9:

Conjugated Proteins

Simple proteins and protein complexes contain only amino acids. In contrast, many other proteins, called conjugated proteins, covalently bond with non-protein moieties.

Nucleoproteins are protein complexes that contain nucleic acids, categorized as deoxyribonucleoproteins (DNPs) or ribonucleoproteins (RNPs) respectively. The nucleosome is a typical example of a DNP where nuclear DNA is associated with histone proteins. The major antigen for the Covid-19 virus SARS-CoV is an RNP that is critical for virus genome replication.

Glycoproteins are conjugated proteins typically located on the surface of cells. Their short carbohydrate chain consists of sugar residues that project outwards from the cell. The carbohydrate domain is essential for cell-cell adhesion, cellular recognition, and signal transduction.

Lipoproteins are protein conjugates with a protein shell over a lipid core that contains cholesterol, triglycerides, or both. Mammalian lipoproteins facilitate the mass transfer of insoluble lipids between their synthesis sites in the liver to other cells. There are several types of lipoproteins categorized by their densities. When the amount of one or more lipoproteins becomes too high, a fraction of the complex becomes insoluble. The insoluble lipoproteins can deposit and block the coronary artery, leading to stroke or heart attack.

Some other conjugated protein types include phosphoproteins, hemoproteins, flavoproteins, metalloproteins, phytochromes, cytochromes, and opsins. Hemoglobin, responsible for oxygen transport in blood vessels, is a conjugate protein that contains iron in its heme prosthetic group.

Suggested Reading

  1. Rappuoli, Rino, Ennio De Gregorio, and Paolo Costantino. "On the mechanisms of conjugate vaccines." Proceedings of the National Academy of Sciences 116, no. 1 (2019): 14-16.
  2. Davis, Benjamin G. "Synthesis of glycoproteins." Chemical reviews 102, no. 2 (2002): 579-602.
  3. Hoofnagle, Andrew N., and Jay W. Heinecke. "Lipoproteomics: using mass spectrometry-based proteomics to explore the assembly, structure, and function of lipoproteins." Journal of lipid research 50, no. 10 (2009): 1967-1975.
  4. Zeng, Weihong, Guangfeng Liu, Huan Ma, Dan Zhao, Yunru Yang, Muziying Liu, Ahmed Mohammed et al. "Biochemical characterization of SARS-CoV-2 nucleocapsid protein." Biochemical and biophysical research communications (2020).