Question

A portion of a polypeptide chain contains the following sequence of amino acids: \- Leu \(-\) Val - Cys - Asp - a. Which amino acids can form a disulfide cross-link? b. Which amino acids are likely to be found on the inside of the protein structure? Why? c. Which amino acids would be found on the outside of the protein? Why? d. How does the primary structure of a protein affect its tertiary structure?

Short answer

a) Cysteine. b) Leucine, Valine, because they are hydrophobic. c) Cysteine, Aspartic acid, due to their tendency to interact with the aqueous environment. d) Primary structure determines tertiary structure through side chain interactions.

Step-by-step solution

Identify Amino Acid Capable of Forming Disulfide Bonds

Cysteine (Cys) is the only amino acid in the sequence capable of forming disulfide cross-links. Disulfide bonds occur between the -SH (thiol) groups of two cysteine molecules.

Determine Amino Acids Likely Found Inside the Protein

Leucine (Leu) and Valine (Val) are nonpolar, hydrophobic amino acids. They are likely to be found on the inside of the protein structure because hydrophobic amino acids tend to avoid water and are stabilized by hydrophobic interactions in the interior.

Determine Amino Acids Likely Found Outside the Protein

Cysteine (Cys) and Aspartic acid (Asp) are more likely to be found on the exterior of the protein. Cysteine can form disulfide bonds with other cysteines either within the same polypeptide chain or between different chains. Aspartic acid is hydrophilic and negatively charged at physiological pH; it can interact with the aqueous environment or other polar molecules.

Understand the Effect of Primary Structure on Tertiary Structure

The primary structure of a protein, which is the linear sequence of amino acids, directly determines its tertiary structure. The interactions between the side chains of the amino acids (e.g., hydrophobic interactions, ionic bonds, hydrogen bonds, and disulfide bonds) drive the folding and final 3D conformation of the protein.

Key concepts

Amino Acids

Amino acids are the building blocks of proteins. They consist of a central carbon (alpha carbon) bonded to four groups: an amino group \( (-NH_2) \), a carboxyl group \( (-COOH) \), a hydrogen atom, and an R-group (side chain) that varies among different amino acids. The properties of proteins are largely determined by the R-groups, which can be nonpolar, polar, charged, or uncharged. This diversity allows proteins to fold into complex structures and perform a wide range of functions in the body.

In the provided polypeptide chain sequence, we see four amino acids: leucine (Leu), valine (Val), cysteine (Cys), and aspartic acid (Asp). Each of these amino acids has distinct characteristics due to their side chains, which influence their role in proteins.

Disulfide Bonds

Disulfide bonds are covalent bonds that form between the sulfur atoms in the side chains of two cysteine molecules. These bonds are represented by \( -S-S- \) and are crucial for stabilizing the three-dimensional structure of proteins. Disulfide bonds help maintain the protein's shape by creating strong links between different parts of the polypeptide chain, which is vital for the protein's function.

In the given sequence (Leu-Val-Cys-Asp), cysteine (Cys) is the only amino acid that can form a disulfide bond. This bond can form within the same protein molecule or between two separate protein chains, contributing significantly to the protein’s stability and its folded structure.

Hydrophobic and Hydrophilic Interactions

Proteins exist in aqueous environments, making hydrophobic and hydrophilic (water-loving) interactions crucial for their structure. Hydrophobic interactions occur between nonpolar amino acids, which tend to cluster together away from water. These interactions help to stabilize the inner core of the protein.

In the sequence (Leu-Val-Cys-Asp), Leucine (Leu) and Valine (Val) are nonpolar and thus hydrophobic. They will likely be found on the inside of the protein, where they can avoid contact with water. On the other hand, hydrophilic interactions involve polar or charged amino acids interacting with water. Cysteine (Cys) and Aspartic acid (Asp) are more hydrophilic. Aspartic acid (Asp), being negatively charged, is especially likely to be found on the protein's exterior, interacting with the aqueous environment or other polar molecules.

Primary Structure

The primary structure of a protein is its unique sequence of amino acids. This linear sequence determines the protein's final three-dimensional shape. Each amino acid in the chain influences how the protein will fold through various interactions, including hydrophobic interactions, hydrogen bonds, ionic bonds, and disulfide bonds.

For example, in the sequence (Leu-Val-Cys-Asp), the specific order and properties of these amino acids dictate how the polypeptide will fold and the final structure it will adopt. Hydrophobic interactions between Leu and Val drive them to the protein’s interior, while interactions involving Cys and Asp contribute to surface properties or form critical cross-links. The precise arrangement of these interactions ensures that the protein achieves the correct conformation to function correctly.