The<unk>  is a 33-residue motif in proteins consisting of two alpha helices separated by loops, first discovered in signaling proteins in yeast Cdc10 and Drosophila Notch.<unk> s mediate protein-protein interactions and are among the most common structural motifs in known proteins. They appear in bacterial, archaeal, and eukaryotic proteins, but are far more common in eukaryotes. Most proteins that contain the motif have four to six<unk> s, although its namesake<unk>  contains 24 and the largest known number of<unk> s is 34, predicted in a protein expressed by Giardia lamblia.
The<unk>  sequence motif has been studied using multiple sequence alignment to determine which conserved amino acid residues are critical for folding and stability. The residues that appear on the wide lateral surface of<unk>  structures are variable, often hydrophobic, and involved mainly in mediating protein-protein interactions. An artificial protein design based on a  consensus sequence derived from sequence alignment has been synthesized and found to fold stably, representing the first designed protein with multiple identical<unk> s. More extensive design strategies have used combinatorial sequences to "evolve"<unk>  motifs that specifically recognize particular protein targets, a technique that has been presented as a possible alternative to antibody design for applications requiring high-affinity binding.<unk>  proteins present an unusual problem in the study of protein folding, which has largely focused on globular proteins that form well-defined tertiary structure stabilized by long-range, nonlocal residue-residue contacts.<unk> s, by contrast, contain very few such contacts (that is, they have a low contact order). Most studies have found that<unk> s fold in a two-state folding mechanism, suggesting a high degree of folding cooperativity despite the local inter-residue contacts and the evident need for successful folding with varying numbers of<unk> s. Some evidence, based on synthesis of truncated versions of natural<unk>  proteins and on the examination of phi values, suggests that the C-terminus forms the folding nucleation site.<unk>  proteins have been associated with a number of human diseases; most notably, the cell cycle inhibitor p16 is associated with cancer and the Notch protein is a key component of cell signaling pathways whose intracellular<unk>  domain is disrupted in mutations that give rise to the neurological disorder known as CADASIL. A specialized family of<unk>  proteins known as muscle<unk>  proteins (MARPs) are involved with the repair and regeneration of muscle tissue following damage due to injury and stress.
Ankyrin repeat
SUMO protein
TORCH complex
Ribosomal RNA
CARD domain
SNARE 
Segrosome
Sarcomere