Proline Residues in Proteins


As the only commonly occurring imino acid in proteins, proline has been found to play unique structural and dynamic roles in guiding protein folding, fibre formation and protein–protein interactions. The cyclic pyrrolidine side‐chain fixes the backbone dihedral ϕ angle and renders proline unable to act as a hydrogen bond donor. These properties are reflected in its preference for protein secondary structure elements such as turns and polyproline II helices, and its generally destabilizing effect on α helix and β‐strand conformation. The ability of proline to undergo cis‐trans isomerization is important in protein folding and forms the basis of molecular switches that help to control cellular growth and regulation. Proline and its posttranslationally modified analogue, hydroxyproline, are additionally the major components of collagens, proteins that are the major fibrous proteins in animals and account for approximately 30% of total human body protein.

Key Concepts:

  • The structural and dynamic properties imparted to proteins by the amino acid proline arise from the unique cyclic structure of its side‐chain.

  • Interconversion of proline from cis to trans conformation, which can be facilitated by peptidylprolyl isomerases, is a rate‐limiting step in protein folding and can act as a molecular switch in the regulation of cellular growth and signalling.

  • Proline residues facilitate the formation of protein secondary structure elements such as turns and the polyproline II helix, but typically disfavour α helix and β‐strand conformations.

  • Proline and its posttranslationally modified analogue hydroxyproline are key components of the structural protein collagen.

  • Regions of water‐soluble proteins rich in proline residues are often sites of protein–protein interaction.

Keywords: proline; hydroxyproline; collagen; polyproline II helix; protein–protein interactions; peptidylprolyl isomerase

Figure 1.

Chemical structures of (a) a proline (Pro) residue and (b) a hydroxyproline (Hyp) residue.

Figure 2.

The nature of Pro interactions and its properties in an α helix. The Pro residue unit is highlighted in the shaded area. The nitrogen (N), carbonyl oxygen (O) and pyrrolidine ring carbons (Greek letters) are indicated, as are the standard protein backbone angles (ϕ, ψ). The full diagram depicts the Pro residue as part of a segment of a helix, with atoms of the other amino acid residues shown in black (carbon), dark grey (oxygen) and light grey (nitrogen). The specific properties and characteristics conferred by a Pro residue on the overall structure are described in the text within the diagram.

Figure 3.

Representation of the different levels of collagen structure. (a) Chemical structure of glycyl‐prolyl‐hydroxyprolyl (Gly‐Pro‐Hyp), the most common tripeptide in the repeating Gly‐X‐Y triad sequence. (b) The molecular conformation of the collagen triple‐helix. (c) Diagram of the axial arrangement of collagen molecules in typical collagen fibrils. Adjacent molecules are staggered axially by 67 nm, generating an axial repeat that can be seen in the electron micrograph of the collagen fibril shown. Each 67 nm repeat contains a dark band (gap region) and a light band (overlap region).



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Deber, Charles M, Brodsky, Barbara, and Rath, Arianna(Apr 2010) Proline Residues in Proteins. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0003014.pub2]