Folding motifs

Alpha proteins

• Four helix bundle: 4 α-helices packed together, can be parallel (cytochrome c) or antiparallel (HGF); highly hydrophobic to stabilise the bundle, using the “ridges-into-groove” model

• Globin fold: 8 α-helices (A-H) arranged in a specific 3D orientation to form a hydrophobic pocket to hold a prosthetic group (like Heme) for active sites.

  • Example: Myoglobin is one globin fold, whilst Haemoglobin is 4 globin folds

Alpha/beta proteins

• TIM barrel: min. 200 residues, 8 parallel β-strands forma central twisted barrel (core) surrounded by 8 α-helices on the periphery, forming a barrel-like shape; active site is at the C-terminal end of the β-strands (the top of the barrel)

• Rossman fold: 6 central, twisted β-sheets with α-helices on both sides. Has a “switch point” where the strand order reverses, creating a crevice where the active site is; classic motif for nucleotide binding

Beta proteins

• Greek key barrel: strands oriented in a specific “folded over” topology

• Up-and-down barrel: simple antiparallel strands connected by loops

What is the Jelly roll barrel?

A beta protein motif.

• “Wrapped” version of Greek key, where the N- & C-terminals always end up close

What is immunoglobulin fold?

A beta protein motif.

• Two antiparallel β-sheets packed against each other (like a sandwich); Y-shaped, the loop at the tips are the antigen-binding sites

What is β-propeller motif?

A beta protein motif.

• Sheets arranged like the blades of a fan around a central axis

What is parallel β-helix?

A beta protein motif.

• Strands wind in a helical fashion to form a triangular prism

• “Toblerone” motif

What is a DNA binding protein motif?

Helix-turn-helix

• Two α-helices connected by a short “turn” of amino acids

• One of the helices fits into the major groove of the DNA

• Most DNA-binding proteins function as dimers