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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
