Nucleic acid encoding chimeric IL-1 receptor type I antagonists
Featured herein are non-naturally occurring cytokine domains that can be used, inter alia, to modulate cellular signalling responsive to interleukin-1 receptor I (IL-1RI), to treat disorders, and to detect and/or bind to cellular receptors, as well as other agents. Exemplary cytokine domains can contain amino acid residues from at least two parental cytokines domains, for example, receptor binding features, surface features, β strands, and loops from at least two parental cytokines domains.
1. An isolated nucleic acid comprising a sequence encoding an amino acid sequence at least 95% identical to SEQ ID NO:21.
2. An isolated nucleic acid vector comprising the nucleic acid of claim 1 , wherein the sequence is operably linked to a transcription control sequence.
3. A recombinant host cell comprising a recombinant isolated nucleic acid according to claim 1 .
4. The host cell of claim 3 that is an E. coli host cell.
5. The isolated nucleic acid of claim 1 , wherein the amino acid sequence has 7 or fewer substitutions relative to SEQ ID NO:21.
6. The isolated nucleic acid of claim 1 , wherein the amino acid sequence has 6 or fewer substitutions relative to SEQ ID NO:21.
7. The isolated nucleic acid of claim 1 , wherein the amino acid sequence has 5 or fewer substitutions relative to SEQ ID NO:21.
8. The isolated nucleic acid of claim 1 , wherein the amino acid sequence has 4 or fewer substitutions relative to SEQ ID NO:21.
9. The isolated nucleic acid of claim 1 , wherein the amino acid sequence has 3 or fewer substitutions relative to SEQ ID NO:21.
10. The isolated nucleic acid of claim 1 , wherein the amino acid sequence has 2 or fewer substitutions relative to SEQ ID NO:21.
11. The isolated nucleic acid of claim 1 , wherein the amino acid sequence has 1 substitution relative to SEQ ID NO:21.
12. The isolated nucleic acid of claim 1 , wherein the amino acid sequence has 7 or fewer non-conservative substitutions relative to SEQ ID NO:21.
13. The isolated nucleic acid of claim 1 , wherein the amino acid sequence has 6 or fewer non-conservative substitutions relative to SEQ ID NO:21.
14. The isolated nucleic acid of claim 1 , wherein the amino acid sequence has 5 or fewer non-conservative substitutions relative to SEQ ID NO:21.
15. The isolated nucleic acid of claim 1 , wherein the amino acid sequence has 4 or fewer non-conservative substitutions relative to SEQ ID NO:21.
16. The isolated nucleic acid of claim 1 , wherein the amino acid sequence has 3 or fewer non-conservative substitutions relative to SEQ ID NO:21.
17. The isolated nucleic acid of claim 1 , wherein the amino acid sequence 2 or fewer non-conservative substitutions relative to SEQ ID NO:21.
18. The isolated nucleic acid of claim 1 , wherein the amino acid sequence has 1 non-conservative substitution relative to SEQ ID NO:21.
19. The isolated nucleic acid of claim 1 , wherein the amino acid sequence consists of a single polypeptide chain that is 150-156 amino acids in length.
20. The isolated nucleic acid of claim 1 , further comprising a sequence encoding a hexa-histidine tag.
21. The isolated nucleic acid of claim 1 , wherein the amino acid sequence is at least 98% identical to SEQ ID NO:21.
22. The isolated nucleic acid of claim 1 , further comprising a sequence encoding a hexa-histidine tag.
23. The isolated nucleic acid of claim 1 , consisting of a sequence encoding an amino acid sequence at least 95% identical to SEQ ID NO:21.
24. An isolated nucleic acid comprising a sequence encoding SEQ ID NO:21.
25. An isolated nucleic acid comprising a sequence at least 95% identical to SEQ ID NO:29 and encoding an amino acid sequence at least 95% identical to SEQ ID NO:21.
26. The isolated nucleic acid of claim 25 , wherein the sequence is at least 98% identical to SEQ ID NO:29.
27. The isolated nucleic acid of claim 25 , wherein the sequence is identical to SEQ ID NO:29.
28. An isolated nucleic acid vector comprising the nucleic acid of claim 25 , wherein the sequence is operably linked to a transcription control sequence.
29. A recombinant host cell comprising a recombinant isolated nucleic acid according to claim 25 .