page_title: Beta hairpin
section_title: Folding and binding dynamics
hierarchical_section_title: Beta hairpin / Folding and binding dynamics
caption_attribution_description: English: Pin1 wwdomain
context_page_description: The beta hairpin is a simple protein structural motif involving two beta strands that look like a hairpin. The motif consists of two strands that are adjacent in primary structure, oriented in an antiparallel direction, and linked by a short loop of two to five amino acids. Beta hairpins can occur in isolation or as part of a series of hydrogen bonded strands that collectively comprise a beta sheet.
  Researchers such as Francisco Blanco et al. have used protein NMR to show that beta-hairpins can be formed from isolated short peptides in aqueous solution, suggesting that hairpins could form nucleation sites for protein folding.
context_section_description: Understanding the mechanism through which micro-domains fold can help to shed light onto the folding patterns of whole proteins. Studies of a beta hairpin called chignolin (see Chignolin on Proteopedia) have uncovered a stepwise folding process that drives beta-hairpin folding. This hairpin has sequence features similar to over 13,000 known hairpins, and thus may serve as a more general model for beta hairpin formation. The formation of a native turn region signals the folding cascade to start, where a native turn is one that is present in the final folded structure.
  In the folding of overall proteins, the turn may originate not in the native turn region but in the C-strand of the beta-hairpin. This turn then propagates through the C-strand (the beta strand leading to C-terminus) until it reaches the native turn region. Sometimes the residue interactions leading up to the native turn region are too strong, causing reverse propagation. However, once the native turn does form, interactions between prolines and tryptophan residues (seen in image at right) in the region help to stabilize the turn, preventing "roll back" or dissolution.
  Researchers believe that turns do not originate in the N-strand, due to increased rigidity (often caused by a proline leading up to the native turn region) and less conformational options. The initial turn formation takes place in about 1 μs. Once the initial turn has been established, two mechanisms have been proposed as to how the rest of the beta-hairpin folds: a hydrophobic collapse with side-chain level rearrangements, or the more accepted zipper-like mechanism.
  The β-hairpin loop motif can be found in many macromolecular proteins. However, small and simple β-hairpins can exist on their own as well. To see this clearly, the Pin1 Domain protein is shown to the left as an example.
  Proteins that are β-sheet rich, also called WW domains, function by adhering to proline-rich and/or phosphorylated peptides to mediate protein–protein interactions. The "WW" refers to two tryptophan (W) residues that are conserved within the sequence and aid in the folding of the β-sheets to produce a small hydrophobic core. These tryptophan residues can be seen below (right) in red.
  This enzyme binds its ligand through van der Waals forces of the conserved tryptophans and the proline-rich areas of the ligand. Other amino acids can then associate with the hydrophobic core of the β-hairpin structure to enforce secure binding.
  It is also common to find proline residues within the actual loop portion of the β-hairpin, since this amino acid is rigid and contributes to the "turn" formation. These proline residues can be seen as red side chains in the image of the Pin1 WW domain below (left).
caption: Pin1 wwdomain-Conserved Tryptophans
exif: {}