Beta-propeller

Toroid protein structure formed from beta sheets

In structural biology, a beta propeller (β propeller) is a type of all β protein architecture characterized by 4 to 8 highly symmetrical blade shaped beta sheets arranged toroidally around a central axis. Together the beta sheets form a funnel like active site.

Each beta sheet typically has four anti parallel β strands arranged in the beta zigzag motif. The strands are twisted so that the first and fourth strands are almost perpendicular to each other. There are five classes of beta propellers, each arrangement being a highly symmetrical structure with 4–8 beta sheets, all of which generally form a central tunnel that yields pseudo symmetric axes. Many beta propellers are dependent on CCT for expression. In at least one case, ions have been shown to increase stability by binding deep in the central tunnel of the beta propeller. According to this model the seven bladed propeller was the most favored arrangement in geometric terms. Despite its highly conserved nature, beta propellers are well known for their plasticity. Beyond having a variety of allowed beta sheets per domain, it can also accommodate other domains into its beta sheets. Additionally, there are proteins that have shown variance in the number of beta strands per beta sheet. Rather than having the typical four beta strands in a sheet, beta lactamase inhibitor protein II only has three beta strands per sheet while the phytase of Bacillus subtilis has five beta strands per beta sheet. The function of the propeller can vary based on the blade number. Four bladed beta propellers function mainly as transport proteins, and because of its structure, they have a conformation that is favorable for substrate binding. Familial hypercholesterolemia is a human genetic disease caused by mutations to the gene that encodes low density lipoprotein receptor (LDLR), a protein which has at least one beta propeller. This disease causes increased concentrations of low density lipoprotein (LDL) and cholesterol which can lead to further consequences such as coronary atherosclerosis. Confirmed mutations have been shown to interfere with hydrogen bonding between blades of the beta propeller. It is one of two proteins present in the viral envelope and catalyzes the cleavage of sialic acid moieties from cell membrane proteins to aid in the targeting of newly produced virions to previously uninfected cells. WD40 repeats, also known as beta transducin repeats, are short fragments found primarily in eukaryotes. They usually form beta propellers with 7–8 blades, but have also been shown to form structural domains with 4 to 16 repeated units critical for protein–protein interactions. WD40 protein motifs are involved in a variety of functions including signal transduction, transcription regulation, and regulation of the cell cycle. They also work as sites for protein protein interactions, and can even play a role in the assembly of protein complexes. Specificity of these structural domains are determined by the sequence of the protein outside of itself. A beta propeller is a critical component of LDLR and aids in a pH based conformational change. At neutral pH the LDLR is in an extended linear conformation and can bind ligands (PCSK9). At acidic pH the linear conformation changes to a hairpin structure such that ligand binding sites bind to the beta propeller, preventing ligand binding. Beta propeller phytases consist of a six bladed β propeller structure. Phytases are phosphatases that can hydrolyze the ester bonds of phytate, the major form of phosphate storage in plants. Through this process, phosphate that is normally inaccessible to livestock becomes available. Most livestock feed has added inorganic phosphate, which when excreted, can cause environmental pollution. The addition of phytase instead of phosphate into livestock feed would allow for animals to break down the phosphate already available in the plant matter. This would theoretically produce less pollution as less of the excess phosphate would be excreted.

Repeat domains known to fold into a beta propeller include WD40, YWTD, Kelch, YVTN, RIVW (PD40), and many more. Their sequences tend to group together, suggesting a close evolutionary link. They are also related to many beta containing domains.