Intro to Systems Biology

Proteins and Nucleic Acids: A background

Crucial to understanding the work done by systems biologists, is knowledge of the four levels of protein structure. Scientists use various tools, which will be discussed later in this lesson, to determine all levels of protein structure.

Illustrations of the four levels of protein structures.

Let’s look at each level of protein structure in detail:

Primary Structure

The primary structure of a protein is its amino acid sequence, which is determined by the gene encoding the protein. This sequence dictates how the protein will fold and function.

Secondary Structure

Secondary structure refers to the local folded structures that form within a polypeptide due to interactions between atoms of the backbone. The most common secondary structures are alpha-helices and beta-sheets.

• Alpha-helix: A right-handed coil where each amino acid forms a hydrogen bond with the amino acid four residues ahead.

• Beta-sheet: A sheet-like arrangement where strands are connected laterally by at least two or three backbone hydrogen bonds, forming a "pleated" sheet.

Tertiary Structure

The tertiary structure is the overall 3D structure of a single polypeptide chain. This level of structure is stabilized by various interactions, including hydrogen bonds, ionic bonds, Van der Waals forces, and hydrophobic interactions.

Quaternary Structure

Quaternary structure refers to the assembly of multiple polypeptide subunits into a larger functional complex. Hemoglobin is a classic example, consisting of four subunits.

Nucleic Acid Structure

Nucleic acids, such as DNA (deoxyribonucleic acid) and RNA (ribonucleic acid), are fundamental molecules that store and transmit genetic information in living organisms.

DNA Structure

DNA (deoxyribonucleic acid) consists of two long strands forming a double helix. Each strand is composed of a sugar-phosphate backbone with nitrogenous bases (adenine, thymine, cytosine, and guanine) attached. The bases pair specifically (adenine with thymine, and cytosine with guanine) through hydrogen bonds, which stabilizes the double helix.

• Double Helix: The two strands of DNA run in opposite directions (antiparallel) and twist around each other, forming a helical structure.

• Base Pairing: Hydrogen bonds between complementary bases (A-T and C-G) hold the two strands together.

This animation shows a molecule of mRNA, created using Rasmol, a free software.

Diagram of DNA double helix structure.

RNA Structure

RNA (ribonucleic acid) is typically single-stranded and plays various roles in coding, decoding, regulation, and expression of genes. Unlike DNA, RNA contains the sugar ribose and the base uracil instead of thymine.

• Single-Stranded: RNA is usually single-stranded but can form secondary structures, such as hairpins and loops, through intramolecular base pairing.

• Functional Diversity: Different types of RNA (e.g., mRNA, tRNA, rRNA) have distinct structures and functions in the cell.

Nucleic acids have primary, secondary, tertiary, and quaternary levels of structure, similar to proteins. Let's examine each level:

1. Primary Structure: The primary structure of nucleic acids refers to the linear sequence of nucleotides linked together by phosphodiester bonds. This sequence is typically written from the 5' end to the 3' end and determines the overall structure and function of the nucleic acid.

2. Secondary Structure: The secondary structure of nucleic acids involves the interactions between bases, primarily through hydrogen bonding. The most well-known secondary structure is the DNA double helix, where two complementary strands are held together by hydrogen bonds between base pairs. In RNA, secondary structures can include stem-loops, hairpins, and other folded conformations.

3. Tertiary Structure: The tertiary structure refers to the three-dimensional shape of the entire nucleic acid molecule. This level of structure involves interactions between different regions of the molecule and can include complex folding patterns, especially in RNA molecules.

4. Quaternary Structure: The quaternary structure involves the to interactions between multiple nucleic acid molecules or between nucleic acids and proteins.

It's important to note that while nucleic acids and proteins share this hierarchical structural organization, the specific factors determining each level of structure differ between the two types of biomolecules. For nucleic acids, base pairing and the sugar-phosphate backbone play crucial roles in determining structure, whereas in proteins, amino acid interactions and peptide bonds are key factors.

Summary of nucleic acid structure using the examples of VS Ribozyme and Telomerase. Image credit: Thomas Shafee