Interleukin-17 receptor (IL-17R) is a cytokine receptor

Cytokine receptor

Cytokine receptors are receptors that bind cytokines.In recent years, the cytokine receptors have come to demand the attention of more investigators than cytokines themselves, partly because of their remarkable characteristics, and partly because a deficiency of cytokine receptors has now been...

 which binds interleukin 17

Interleukin 17

Interleukin-17 is the founding member of a group of cytokines called the IL-17 family. IL-17A, was originally identified as a transcript from a rodent T-cell hybridoma by Rouvier et al. in 1993...

. Functional IL-17R is a heteromeric complex consisting of at least IL17RA

IL17RA

Interleukin 17 receptor A, also known as IL17RA and CDw217 , is a human gene....

 and IL17RC

IL17RC

Interleukin-17 receptor C is a protein that in humans is encoded by the IL17RC gene....

.

A number of additional variants exist including IL17RB

IL17RB

Interleukin-17 receptor B is a protein that in humans is encoded by the IL17RB gene....

, which binds preferentially IL17B and IL17E

Interleukin 25

Interleukin-25 is a protein that in humans is encoded by the IL25 gene.- Function :IL-25 is a cytokine that shares the sequence similarity with IL17. This cytokine can induce NF-κB activation, and stimulate the production of IL8. Both this cytokine and IL17B are ligands for the cytokine receptor...

. A total of five members of the family have been identified. The first identified member, IL-17RA is located on human chromosome 22.

Evolution

There are two IL17Rs (IL17RA and IL17RD) in the genome of the basal chordate Amphioxus. After two rounds of whole genome duplications, these two IL17R genes expanded into five early vertebrate IL17R genes, IL17RA to IL17RE. Two (IL17RA and IL17RD) are found in most vertebrates, whereas the other three (IL17RB, ILR17RC and IL17RE) have undergone some losses in vertebrates during evolution.

Structure

IL-17A and IL-17RA are founding members of a new subfamily receptors A-F. IL-17RA is by far the largest member of the family and has the largest cytoplasmic tail of the family. This cytoplasmic tail provides docking sites for numerous signaling intermediates. IL-17RA is composed of both alpha helices

Alpha helix

A common motif in the secondary structure of proteins, the alpha helix is a right-handed coiled or spiral conformation, in which every backbone N-H group donates a hydrogen bond to the backbone C=O group of the amino acid four residues earlier...

 and beta sheet

Beta sheet

The β sheet is the second form of regular secondary structure in proteins, only somewhat less common than the alpha helix. Beta sheets consist of beta strands connected laterally by at least two or three backbone hydrogen bonds, forming a generally twisted, pleated sheet...

s and has fibronectin

Fibronectin

Fibronectin is a high-molecular weight glycoprotein of the extracellular matrix that binds to membrane-spanning receptor proteins called integrins. In addition to integrins, fibronectin also binds extracellular matrix components such as collagen, fibrin and heparan sulfate proteoglycans...

 domains, beta-sandwich

Beta barrel

A beta barrel is a large beta-sheet that twists and coils to form a closed structure in which the first strand is hydrogen bonded to the last.Beta-strands in beta-barrels are typically arranged in an antiparallel fashion...

 domains, and ectodomain

Ectodomain

An ectodomain is the domain of a membrane protein that extends into the extracellular space . Ectodomains are usually the part of a protein that initiate contact with surface which leads to signal transduction. In SARS-CoV the ectodomain of the spike protein is responsible for attachment to and...

s.

Clinical significance

IL-17A neutralizing antibodies have the potential for the treatment of autoimmune diseases in humans. It also may soon be used for protection against periodontal bone loss as it is currently being tested in mice. IL-17 RA has been observed at high levels in people undergoing treatment for cardiac fibroblasts and in certain tissues such as: haematopoietic, bone marrow, thymus, and spleen tissue. IL-17 RA is also normally found in low levels in colon, small intestine, and lung tissues.

External links

• 'http://www.rcsb.org/pdb/explore/explore.do?structureId=3JVF'