2oqp

From Proteopedia

Solution structure of human interleukin-21

Structural highlights

2oqp is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Solution NMR, 20 models
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

IL21_HUMAN Cytokine with immunoregulatory activity. May promote the transition between innate and adaptive immunity. Induces the production of IgG(1) and IgG(3) in B-cells (By similarity). May play a role in proliferation and maturation of natural killer (NK) cells in synergy with IL15. May regulate proliferation of mature B- and T-cells in response to activating stimuli. In synergy with IL15 and IL18 stimulates interferon gamma production in T-cells and NK cells. During T-cell mediated immune response may inhibit dendritic cells (DC) activation and maturation.^[1] ^[2]

Evolutionary Conservation

Checkto colour the structure by Evolutionary Conservation, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

The high resolution three-dimensional structure of human interleukin (hIL)-21 has been resolved by heteronuclear NMR spectroscopy. Overall, the hIL-21 structure is dominated by a well defined central four-helical bundle, arranged in an up-up-down-down topology, as observed for other cytokines. A segment of the hIL-21 molecule that includes the third helical segment, helix C, is observed to exist in two distinct and interchangeable states. In one conformer, the helix C segment is presented in a regular, alpha-helical conformation, whereas in the other conformer, this segment is largely disordered. A structure-based sequence alignment of hIL-21 with receptor complexes of the related cytokines, interleukin-2 and -4, implied that this particular segment is involved in receptor binding. An hIL-21 analog was designed to stabilize the region around helix C through the introduction of a segment grafted from hIL-4. This novel hIL-21 analog was demonstrated to exhibit a 10-fold increase in potency in a cellular assay.

The existence of multiple conformers of interleukin-21 directs engineering of a superpotent analogue.,Bondensgaard K, Breinholt J, Madsen D, Omkvist DH, Kang L, Worsaae A, Becker P, Schiodt CB, Hjorth SA J Biol Chem. 2007 Aug 10;282(32):23326-36. Epub 2007 Jun 12. PMID:17565991^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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Citations

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References

↑ Parrish-Novak J, Dillon SR, Nelson A, Hammond A, Sprecher C, Gross JA, Johnston J, Madden K, Xu W, West J, Schrader S, Burkhead S, Heipel M, Brandt C, Kuijper JL, Kramer J, Conklin D, Presnell SR, Berry J, Shiota F, Bort S, Hambly K, Mudri S, Clegg C, Moore M, Grant FJ, Lofton-Day C, Gilbert T, Rayond F, Ching A, Yao L, Smith D, Webster P, Whitmore T, Maurer M, Kaushansky K, Holly RD, Foster D. Interleukin 21 and its receptor are involved in NK cell expansion and regulation of lymphocyte function. Nature. 2000 Nov 2;408(6808):57-63. PMID:11081504 doi:http://dx.doi.org/10.1038/35040504
↑ Strengell M, Julkunen I, Matikainen S. IFN-alpha regulates IL-21 and IL-21R expression in human NK and T cells. J Leukoc Biol. 2004 Aug;76(2):416-22. Epub 2004 Jun 3. PMID:15178704 doi:http://dx.doi.org/10.1189/jlb.1003488
↑ Bondensgaard K, Breinholt J, Madsen D, Omkvist DH, Kang L, Worsaae A, Becker P, Schiodt CB, Hjorth SA. The existence of multiple conformers of interleukin-21 directs engineering of a superpotent analogue. J Biol Chem. 2007 Aug 10;282(32):23326-36. Epub 2007 Jun 12. PMID:17565991 doi:10.1074/jbc.M701313200