Pre-Ligand assembly domain of the IL-17 receptor

Abstract

The invention provides isolated Pre-Ligand Assembly Domain (PLAD) polypeptides which inhibit multimerization of a receptor complex comprising an IL-17R family member. Related PLAD-binding polypeptides, chimeric proteins, conjugates, nucleic acids, vectors, host cells, and methods are provided herein.

1 .- 37 . (canceled) 
     
     
         38 . An isolated nucleic acid molecule encoding a soluble polypeptide comprising (i) the amino acid sequence of SEQ ID NO: 4, or an amino acid sequence which is at least 90% identical to SEQ ID NO: 4 and (ii) a secretion signal sequence, wherein the soluble polypeptide lacks a Fibronectin III-like domain 1 (FN1) of an IL-17 receptor A (IL-17RA). 
     
     
         39 . The isolated nucleic acid molecule of  claim 38 , wherein the soluble polypeptide lacks SEQ ID NO: 23. 
     
     
         40 . The isolated nucleic acid molecule of  claim 38 , wherein the secretion signal sequence is a secretion signal sequence of an immunoglobulin. 
     
     
         41 . The isolated nucleic acid molecule of  claim 40 , wherein the secretion signal sequence is a secretion signal sequence of Igx (SEQ ID NO: 16). 
     
     
         42 . The isolated nucleic acid molecule of  claim 38 , comprising a nucleic acid sequence which encodes an expression tag and/or a purification tag. 
     
     
         43 . The isolated nucleic acid molecule of claim  5 , comprising one or more GSS linkers. 
     
     
         44 . The isolated nucleic acid molecule of  claim 38 , comprising a nucleic acid sequence encoding three Cys residues. 
     
     
         45 . The isolated nucleic acid molecule of  claim 38 , comprising a nucleic acid sequence encoding a linker of an IL-17 receptor A (IL-17RA). 
     
     
         46 . The isolated nucleic acid molecule of  claim 45 , wherein the nucleic acid sequence encoding the linker encodes the amino acid sequence of SEQ ID NO: 21. 
     
     
         47 . The isolated nucleic acid molecule of  claim 46 , comprising a nucleic acid sequence encoding the amino acid sequence of SEQ ID NO: 8. 
     
     
         48 . The isolated nucleic acid molecule of  claim 38 , comprising a nucleic acid sequence encoding LWD. 
     
     
         49 . The isolated nucleic acid molecule of  claim 48 , wherein the nucleic acid sequence encoding LWD is (i) 5′ to the nucleic acid sequence encoding the amino acid sequence of SEQ ID NO: 4 or the amino acid sequence which is at least 90% identical to SEQ ID NO: 4 and (ii) 3′ to the secretion signal sequence. 
     
     
         50 . An isolated nucleic acid molecule encoding a chimeric protein comprising a polypeptide comprising (i) the amino acid sequence of SEQ ID NO: 4, or an amino acid sequence which is at least 90% identical to SEQ ID NO: 4, and (ii) a heterologous moiety, wherein the polypeptide lacks a Fibronectin III-like domain 1 (FN1) of an IL-17 receptor A (IL-17RA). 
     
     
         51 . A vector comprising the isolated nucleic acid molecule of  claim 38 . 
     
     
         52 . A vector comprising the isolated nucleic acid molecule of  claim 50 . 
     
     
         53 . A host cell comprising the isolated nucleic acid molecule of  claim 38 . 
     
     
         54 . A host cell comprising the isolated nucleic acid molecule of  claim 50 . 
     
     
         55 . An isolated polypeptide comprising (i) the amino acid sequence of SEQ ID NO: 4, or an amino acid sequence which is at least 90% identical to SEQ ID NO: 4 and (ii) a secretion signal sequence, wherein the secreted/soluble polypeptide lacks a Fibronectin III-like domain 1 (FN 1) of an IL-17 receptor A (IL-17RA). 
     
     
         56 . An isolated PLAD-binding polypeptide which specifically binds to an epitope within SEQ ID NO: 3 or 4 of the PLAD polypeptide, or a functional fragment thereof. 
     
     
         57 . An isolated nucleic acid molecule encoding the PLAD-binding polypeptide of  claim 56 .