Structural Biochemistry/Beta-Propeller Proteins

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Introduction[edit | edit source]

A seven-bladed β-propeller protein.

A beta-propeller is a symmetrical protein that is made with four-stranded antiparallel beta sheets arranged in a circle. The number of antiparallel beta sheets, also known as blades, dictates what function a beta-propeller possesses. Four-, five-, six-, seven-, eight- and ten-bladed beta-propellers and their functionalities are known so far. Beta-propellers are typically shaped like a funnel, where protein-protein interactions can occur on all sides of the funnel, including the central opening. There is a large variety of beta-propellers, all of which are categorized into families that depend on their blade number and amino acid sequence. Some beta-propeller families include: the WD40 family (the largest family of propeller proteins), regulator of chromatin condensation 1 (RCC1) family, kelch family, YWTD family, NHI family, YVTN family, and the Asp-box family.

Function and Structure Association with Number of Blades[edit | edit source]

Four- and five-bladed propellers: Four- and five- bladed propellers have limited variation in functinonality. Four-bladed propellers act as ligand-binding proteins and are repsonsible for transportation and catalysis. The smallest known form of a four-bladed propeller structure is hemopexin, which is a plasma glycoprotein that has heme-binding abilities. Five-bladed propellers are abundant in nature, but only act as transferases, hydrolases, and sugar-binding proteins.

Six- and seven-bladed propellers: Unlike the four- and five-bladed propellers, six- and seven-bladed propellers have a high variation in functionality. Six-bladed propellers act as ligand-binding proteins, hydrolases, lyases, isomerases, signaling proteins, and structural proteins. Seven-bladed propellers act as ligand-binding proteins, hydrolases, lyases, oxidoreductases, signaling proteins, and structural proteins.

Eight- and ten-bladed propellers: Similar to four- and five-bladed propellers, eight- and ten-bladed propellers also have low variation in functionality. Eight-bladed propellers act as oxidoreductases and structural proteins, and ten-bladed propellers act as signaling-proteins. The only well-known 10-bladed propeller is sortillin, which plays an important role in endocytosis and intracellular sorting. Sortillin is unique in that it is able to regulate ligand- binding by only allowing one ligand to bind at a time to prevent ambiguity in functionality.

Newly-Discovered Beta-Propeller: the Beta-Pinwheel[edit | edit source]

A newly-discovered beta-propeller called the beta-pinwheel has been found to have a unique property of having strand exchange in the anti-parallel beta-sheets, giving the beta-pinwheel a Velcro-like characteristic which increases its structural stability. Contrary to regular beta-propellers, where beta-propellers are always in closed-ring form, the beta-pinwheel can be in an open-ring form (open barrel form), where the two blade ends of the broken ring can have no interactions with each other. Beta-pinwheels also vary drastically in blade number; they range from three to eight blades. Although beta-pinwheels have a wide range of blade numbers, they all are limited to one function: DNA-binding.

Beta-Propellers and Human Disease[edit | edit source]

Beta-propellers have been discovered to associate with human diseases when beta-propellers have been mutated. For example, when mutations on the calcium binding pockets of integrin αIIbβ3, a seven-bladed propeller, are present, Glanzmann thrombasthenia (GT), a recessive bleeding disorder, can occur. Kallmann syndrome, a genetic disorder that affects the production of sex hormones, can occur when there are mutations at the protein-protein binding region of WD repeat domain 11 (WDR11) beta-propellers.

References[edit | edit source]

  • Chen, Cammy K.-M.; Chan, Nei-Li; Wang, Andrew H.-J. (2011). "The many blades of the β-propeller proteins: Conserved but versatile". Trends in Biochemical Sciences 36 (10): 553–61. doi:10.1016/j.tibs.2011.07.004. PMID 21924917.