Type II cytokine receptor

Type II cytokine receptor
Identifiers
SymbolType II cytokine receptor
Membranome1030
Interferon gamma receptor
Identifiers
SymbolIFNGR1
PfamPF07140
InterProIPR021126
SCOP21fg9 / SCOPe / SUPFAM
Available protein structures:
PDB  IPR021126 PF07140 (ECOD; PDBsum)  
AlphaFold
Interferon-alpha/beta receptor, fibronectin type III
Identifiers
SymbolInterfer-bind
PfamInterfer-bind
InterProIPR015373
SCOP21n6u / SCOPe / SUPFAM
Available protein structures:
PDB  IPR015373 Interfer-bind (ECOD; PDBsum)  
AlphaFold

Type II cytokine receptors, also commonly known as class II cytokine receptors, are transmembrane proteins that are expressed on the surface of certain cells. They bind and respond to the class II cytokines, which includes all types of interferons[1] and members of the interleukin-10 family[2][3] These receptors are characterized by the lack of a WSXWS motif which differentiates them from type I cytokine receptors.[4]

In the context of fish and animals further removed from humans, the family is also called cytokine receptor family B (CRFB).[5]

Structure

Type II cytokine receptors are related predominantly by sequence similarities in their extracellular portions that are composed of tandem Ig-like (FN3) domains. The structures for the extracellular domains of the receptors for interferon types, I, II, and III are all known.[6] Type II cytokine receptors are tyrosine-kinase-linked receptors. The intracellular domain of type II cytokine receptors is typically associated with a tyrosine kinase belonging to the Janus kinase (JAK family). Binding of the receptor typically leads to activation of the canonical JAK/STAT signaling pathway.[7]

Like other cytokine receptors, many type II CRs are heterodimers or multimers with a high and a low affinity component. The high-affinity component is cytokine‐specific and, again like other CRs, is often the α chain. The low-affinity component remains required for forming a functional complex: in some examples such as IFN III, the ligand first binds to the α chain, then the two molecules together recruits a "shared" β chain.[8]

Typical CRFBs have an alpha chain and a beta chain. Each chain contains two (except for IFNAR1) N-terminal extracellular ligand-binding fibronectin type III domains (FN3; each pair is called a cytokine homology region, CHR), then extends intracellularly. Unlike class I CRs, all chains (even alpha) bind a kinase to participate in signaling. The shorter one (<100 intracellular residues, usually α) typically binds either JAK2 or TYK2, and the longer one typically interacts with JAK1. Interaction with JAK1 is mediated by a conserved motif PxxLxF (box1). There is a neighboring box2 that by itself poorly binds JAK1, but improves the binding between box1 and JAK1 in vitro. C-terminal to the two kinase boxes, mainly on the "long" chain, is a disordered region that binds STAT.[9] TYK2 binding is greatly dependent on box2.[8]

There are many variations on the theme among the type II receptors, including a high-affinity β chain, some non-shared chains, and doubled stoichiometry where the complex is a heterotetramer assembled on binding a heterodimer cytokine (IFN II and IL-10 family members).[8]

Types

Type II cytokine receptors include those that bind interferons and those that bind members of the interleukin-10 family (interleukin-10, interleukin-20, interleukin-22, and interleukin-28).[3][2] Expression of specific receptor varieties is highly variable across tissue types with some receptors being ubiquitously expressed and some receptors only expressed in specific tissues.[4]

Some combinations of human type II cytokine receptors[10][8]
Short nameCytokinesHigh-affinityLow-affinityKinase (Hi, Lo)STATSOCSNotes
IFN I RIFN-αβεκωIFNAR2IFNAR1JAK1, TYK2Stat1, Stat2 → IRF9SOCS1IFNAR1 has two CHRs.
IFN II RIFN-γIFNGR1IFNGR2JAK1, JAK2Stat1SOCS1Doubled.
IFN III R
IL-28R		IFN-λIFNLR1IL10RBTYK2, JAK1Stat1, Stat2 → IRF9SOCS1
IL-10RIL-10IL10RAIL10RBTYK2, JAK1Stat3, Stat1, Stat5?Doubled.
IL-20R, IIIL-19/20/24IL20RB[8]IL20RATYK2, JAK1Stat3, Stat5?β is high-affinity.
IL-20R, IIL-20/24IL22RIL20RBTYK2, JAK1Stat3, Stat5?
IL-22RIL-22IL22RIL10RBTYK2, JAK1Stat3, Stat1, Stat5?May recruit IL-22BP (antagonist).
IL-26RIL-26IL20RAIL10RBTYK2, JAK1Stat3, Stat1?Likely doubled.

Interferon receptors

The interferon receptor is a molecule displayed on the surface of cells which interacts with extracellular interferons. Class II cytokine receptors bind type I, type II, and type III interferons. Type I interferons play important roles in both the adaptive and innate immune responses, prevent proliferation of pathogens, and have antiviral activities. Type II interferons help to modulate the immune system's response to pathogens, and these interferons also respond to pathogens. Type III interferons induce a similar response to type I interferons, but their expression is limited to epithelial cells.[1][4] The receptor is coded for by number of different genes, due to the diversity of types of interferons. Regulation of cell surface receptor levels plays an important role in the regulation and limiting of interferon signaling.

Interleukin receptors

References

  1. 1 2 Krey K, Babnis AW, Pichlmair A (October 2020). "System-Based Approaches to Delineate the Antiviral Innate Immune Landscape". Viruses. 12 (10): 1196. doi:10.3390/v12101196. PMC 7589202. PMID 33096788.
  2. 1 2 Xu W, Presnell SR, Parrish-Novak J, Kindsvogel W, Jaspers S, Chen Z, et al. (August 2001). "A soluble class II cytokine receptor, IL-22RA2, is a naturally occurring IL-22 antagonist". Proceedings of the National Academy of Sciences of the United States of America. 98 (17): 9511–6. Bibcode:2001PNAS...98.9511X. doi:10.1073/pnas.171303198. PMC 55483. PMID 11481447.
  3. 1 2 Dumoutier L, Lejeune D, Hor S, Fickenscher H, Renauld JC (March 2003). "Cloning of a new type II cytokine receptor activating signal transducer and activator of transcription (STAT)1, STAT2 and STAT3". The Biochemical Journal. 370 (Pt 2): 391–6. doi:10.1042/BJ20021935. PMC 1223207. PMID 12521379.
  4. 1 2 3 Stanifer ML, Pervolaraki K, Boulant S (March 2019). "Differential Regulation of Type I and Type III Interferon Signaling". International Journal of Molecular Sciences. 20 (6): 1445. doi:10.3390/ijms20061445. PMC 6471306. PMID 30901970.
  5. ↑ Deng, Yu Hang; Li, Bo; Chen, Shan Nan; Ren, Li; Zhang, Bai Dong; Liu, Lan Hao; Liu, Shaojun; Nie, P. (August 2023). "Molecular characterization of nineteen cytokine receptor family B (CRFB) members, CRFB1, CRFB2, CRFB4-17, with three CRFB9 and two CRFB14 in a cyprinid fish, the blunt snout bream Megalobrama amblycephala". Developmental & Comparative Immunology. 145 104725. doi:10.1016/j.dci.2023.104725. PMID 37146740.
  6. ↑ Walter MR (2020). "The Role of Structure in the Biology of Interferon Signaling". Frontiers in Immunology. 11 606489. doi:10.3389/fimmu.2020.606489. PMC 7689341. PMID 33281831.
  7. ↑ Fox LE, Locke MC, Lenschow DJ (2020-12-21). "Context Is Key: Delineating the Unique Functions of IFNα and IFNβ in Disease". Frontiers in Immunology. 11 606874. doi:10.3389/fimmu.2020.606874. PMC 7779635. PMID 33408718.
  8. 1 2 3 4 5 Morris, R; Kershaw, NJ; Babon, JJ (December 2018). "The molecular details of cytokine signaling via the JAK/STAT pathway". Protein Science. 27 (12): 1984–2009. doi:10.1002/pro.3519. PMC 6237706. PMID 30267440.
  9. ↑ Ferrao, R; Wallweber, HJ; Ho, H; Tam, C; Franke, Y; Quinn, J; Lupardus, PJ (7 June 2016). "The Structural Basis for Class II Cytokine Receptor Recognition by JAK1". Structure (London, England : 1993). 24 (6): 897–905. doi:10.1016/j.str.2016.03.023. PMC 4899269. PMID 27133025.
  10. ↑ Ouyang, Wenjun; O'Garra, Anne (2019-04-16). "IL-10 Family Cytokines IL-10 and IL-22: from Basic Science to Clinical Translation". Immunity. 50 (4): 871–891. doi:10.1016/j.immuni.2019.03.020. ISSN 1074-7613. PMID 30995504. S2CID 122350808.
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