7nxz
From Proteopedia
Synthetic glycoform of Human Interleukin 6
Structural highlights
Disease[IL6_HUMAN] Genetic variations in IL6 are associated with susceptibility to rheumatoid arthritis systemic juvenile (RASJ) [MIM:604302]. An inflammatory articular disorder with systemic-onset beginning before the age of 16. It represents a subgroup of juvenile arthritis associated with severe extraarticular features and occasionally fatal complications. During active phases of the disorder, patients display a typical daily spiking fever, an evanescent macular rash, lymphadenopathy, hepatosplenomegaly, serositis, myalgia and arthritis. Note=A IL6 promoter polymorphism is associated with a lifetime risk of development of Kaposi sarcoma in HIV-infected men. Function[IL6_HUMAN] Cytokine with a wide variety of biological functions. It is a potent inducer of the acute phase response. Plays an essential role in the final differentiation of B-cells into Ig-secreting cells Involved in lymphocyte and monocyte differentiation. It induces myeloma and plasmacytoma growth and induces nerve cells differentiation Acts on B-cells, T-cells, hepatocytes, hematopoietic progenitor cells and cells of the CNS. Also acts as a myokine. It is discharged into the bloodstream after muscle contraction and acts to increase the breakdown of fats and to improve insulin resistance. Publication Abstract from PubMedA library of glycoforms of human interleukin 6 (IL-6) comprising complex and mannosidic N-glycans was generated by semisynthesis. The three segments were connected by sequential native chemical ligation followed by two-step refolding. The central glycopeptide segments were assembled by pseudoproline-assisted Lansbury aspartylation and subsequent enzymatic elongation of complex N-glycans. Nine IL-6 glycoforms were synthesized, 7 of which were evaluated for in vivo plasma clearance in rats and compared to non-glycosylated recombinant IL-6 from E. coli. Each IL-6 glycoform was tested in three animals and reproducibly showed individual serum clearances depending on the structure of the N-glycan. The clearance rates were atypical, since the 2,6-sialylated glycoforms of IL-6 cleared faster than the corresponding asialo IL-6 with terminal galactoses. Compared to non-glycosylated IL-6 the plasma clearance of IL-6 glycoforms was delayed in the presence of larger and multibranched N-glycans in most cases. Natural Glycoforms of Human Interleukin 6 show atypical plasma clearance.,Unverzagt C, Reif A, Lam K, Weidler S, Lott M, Boos I, Lokau J, Bretscher C, Monnich M, Perkams L, Schmalzlein M, Graf C, Fischer JP, Lechner C, Hallstein K, Becker S, Weyand M, Steegborn C, Schultheiss G, Rose-John S, Garbers C Angew Chem Int Ed Engl. 2021 Mar 23. doi: 10.1002/anie.202101496. PMID:33756033[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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