Beta hairpin

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A beta hairpin is a simple protein shape made of two beta strands that look like a hairpin. The two strands run next to each other in opposite directions and are held together by a short loop of 2 to 5 amino acids. Beta hairpins can exist on their own or as part of a larger beta sheet. Experiments show that hairpins can form from short pieces of protein in water, suggesting they can help start the folding of bigger proteins.

Classification and structure
- Originally, hairpins were named by the number of residues in the loop, but this didn’t capture how the ends are bonded.
- A clearer system divides beta hairpins into four classes, based on loop size and the pattern of hydrogen bonds at the ends. Each class starts with a small loop and can grow by changing the hydrogen bonds.
- Whether the end residues are single- or doubly bonded matters. If residues are added or removed, the hairpin may need to unfold and refold, which can change its class.

Folding and behavior
- The first turn that defines the hairpin forms quickly, in about 1 microsecond.
- After the turn forms, the rest of the hairpin can fold two main ways:
- A hydrophobic collapse where side chains crowd together.
- A zipper-like mechanism that aligns the two strands step by step.

Biological roles and design ideas
- Beta hairpins appear in many proteins and are common building blocks of beta-sheet-rich domains.
- Some domains, like WW domains, bind other molecules using conserved tryptophan residues that help create a compact hydrophobic core and stabilize the hairpin.
- Proline residues are often found in the loop because they help create the sharp turn.

Designing beta-hairpins
- Scientists have learned to create stable beta-hairpins without metals or disulfide bonds. A key trick is using cross-strand tryptophan pairs (Trp-Trp) that act like a zipper to stabilize the fold, allowing stable hairpins with about 12 amino acids that stay water-soluble.
- Another tool is the tryptophan zipper (trpzip) peptide, studied by NMR, which shows how these interactions stabilize the structure.
- Some designs add photoswitches like azobenzene in the turn area. Light can switch the molecule between forms that do and do not fold into a beta hairpin, enabling precise control of folding with light.

In short, beta hairpins are tiny, versatile folds that help turn linear peptides into stable, functional structures, and they’re a key focus for understanding protein folding and designing new peptides.