As described in this chapter, proline introduces kinks in transmembrane \(\alpha\) -helices. What are the molecular details of the kink, and why does it form? A good reference for this question is von Heijne, G. 1991\. Proline kinks in transmembrane \(\alpha\) -helices. Journal of Molecular Biology \(218: 499-503 .\) Another is Barlow, D. \(\mathrm{J}\)., and Thornton, J. M., \(1988 .\) Helix geometry in proteins. Journal of Molecular Biology \(201: 601-619\)

Understanding the secondary structure of proteins is crucial for grasping how proteins fold and function. At this level, proteins exhibit repetitive patterns like alpha helices and beta sheets. The alpha helix is a right-handed coil where each turn of the helix is stabilized by hydrogen bonds between the backbone atoms. The hydrogen bonds form between the carbonyl oxygen of one amino acid and the amide hydrogen four residues earlier in the sequence.

• Stability of alpha helices is determined by the sequence of amino acids.
• Changes in the amino acid sequence can affect the hydrogen bonding pattern, impacting the helix structure.
• Alpha helices are common in transmembrane regions of proteins, facilitating their integration into the lipid bilayer.

Alpha helices are essential to the protein's overall 3D structure, dictating how it interacts with other molecules and performs its biological roles.

Amino acids are the building blocks of proteins and each has unique characteristics that influence protein structure and function. The properties of amino acids hinge on their side chains, which vary in size, shape, charge, hydrophobicity, and the ability to form hydrogen bonds.

• Nonpolar amino acids tend to be hydrophobic and prefer to be buried inside protein structures away from water.
• Polar amino acids are typically found on the surface of proteins, making contact with water.
• Charged amino acids often participate in ionic interactions and play roles in protein stability and binding of substrates or ligands.

These varying properties drive protein folding, ultimately determining the protein's shape and function in biological processes.

Proline has a distinct role in membrane proteins, which are often alpha-helical in structure when spanning the lipid bilayer. Membrane proteins are integral to cell signaling and transport, requiring specific conformations for proper function.

• The cyclic side chain of proline makes it hydrophobic, which allows it to be compatible with the lipid bilayer's hydrophobic core.
• The rigid structure of proline disrupts local secondary structures, which can create necessary bends or loops in the protein for precise function.
• Proline <-induced kinks can serve as start or stop signals for helix folding within the bilayer or play roles in forming the correct 3D structures required for protein interaction with other cellular components.

Incorporating proline at key positions can thus significantly influence the structure and role of membrane proteins within the cell environment.

The insertion of proline into an alpha-helix sequence can lead to a disruption or kink in the helix. This stands in contrast with other amino acids, which contribute to the regular, helical structure when part of a polypeptide chain.

• Due to proline's unique ring structure, it is unable to participate in the normal intrachain hydrogen bonding that stabilizes the alpha helix.
• This inability to form a hydrogen bond with the preceding carbonyl group introduces a bend in the helix, altering its direction.
• The kink affects not just the local structure, but also the overall 3D configuration of the protein, which can influence how the protein interacts with other molecules.

Understanding alpha-helix disruptions by proline is essential in predicting protein structure and function, especially in designing drugs and understanding genetic mutations.