Odorant receptors

Abstract

The invention provides methods and compositions relating to odorant receptors, including a general expression cloning methodology which is useful for identifying novel G protein-coupled receptors and a novel family of odorant receptors and related nucleic acids, ligands, agonists and antagonists. These compositions provide a wide variety of applications such as screening for related receptors, and by modulating the function of the disclosed receptors by modulating their expression or contacting them with agonists, antagonist or ligands modulating reproductive/sexual and non-sexual social behaviors mediated via the olfactory system, reproductive physiologies and olfactory system regulated feeding behaviors, migratory behaviors and events such as conception, implantation, estrous and menstruation.

What is claimed is:  
     
         1 . An isolated polypeptide comprising a sequence selected from the group consisting of: 
 SEQ ID NOS:02-06;    at least 16 consecutive residues of a sequence selected from the group consisting of SEQ ID NOS:07, 08, 10, 12 and 14;                                            SEQ ID NO:02, res. 1-10;         SEQ ID NO:02, res. 29-41;         SEQ ID NO:02, res. 75-87;         SEQ ID NO:02, res. 92-109;         SEQ ID NO:02, res. 132-141;         SEQ ID NO:02, res. 192-205;         SEQ ID NO:02, res. 258-269;         SEQ ID NO:02, res. 295-311;         SEQ ID NO:02, res. 316-330;         SEQ ID NO:02, res. 373-382;         SEQ ID NO:02, res. 403-422;         SEQ ID NO:02, res. 436-442;         SEQ ID NO:02, res. 474-485;         SEQ ID NO:02, res. 502-516;         SEQ ID NO:02, res. 561-576;         SEQ ID NO:02, res. 595-616;         SEQ ID NO:02, res. 640-656;         SEQ ID NO:02, res. 683-697;         SEQ ID NO:02, res. 717-732;         SEQ ID NO:02, res. 768-777;         SEQ ID NO:02, res. 798-813;         SEQ ID NO:02, res. 829-843;         SEQ ID NO:02, res. 844-877; and         SEQ ID NO:02, res. 852-875.                                                                    
     
     
         2 . A polypeptide according to  claim 1  comprising at least 16 consecutive residues of SEQ ID NO:02.  
     
     
         3 . A polypeptide according to  claim 1  comprising SEQ ID NO:02, res.1-566.  
     
     
         4 . A polypeptide according to  claim 1  comprising SEQ ID NO:02.  
     
     
         5 . A polypeptide according to  claim 1 , wherein the sequence is SEQ ID NO: 14.  
     
     
         6 . A polypeptide according to  claim 1 , comprising SEQ ID NO: 14.  
     
     
         7 . An isolated or recombinant polynucleotide comprising at least 36 contiguous nucleotides of a strand of a sequence selected from the group consisting of SEQ ID NO 01, 09, 11 and 13.  
     
     
         8 . A polynucleotide according to  claim 7 , comprising a sequence selected from the group consisting of:  
       
         
           
                 
                 
               
                     
                     
                 
                     
                     
                 
                     
                   SEQ ID NO:01, nucl. 1-47; 
                 
                     
                   SEQ ID NO:01, nucl. 58-99; 
                 
                     
                   SEQ ID NO:01, nucl. 95-138; 
                 
                     
                   SEQ ID NO:01, nucl. 181-220; 
                 
                     
                   SEQ ID NO:01, nucl. 261-299; 
                 
                     
                   SEQ ID NO:01, nucl. 274-315; 
                 
                     
                   SEQ ID NO:01, nucl. 351-389; 
                 
                     
                   SEQ ID NO:01, nucl. 450-593; 
                 
                     
                   SEQ ID NO:01, nucl. 524-546; 
                 
                     
                   SEQ ID NO:01, nucl. 561-608; 
                 
                     
                   SEQ ID NO:01, nucl. 689-727; 
                 
                     
                   SEQ ID NO:01, nucl. 708-737; 
                 
                     
                   SEQ ID NO:01, nucl. 738-801; 
                 
                     
                   SEQ ID NO:01, nucl. 805-854; 
                 
                     
                   SEQ ID NO:01, nucl. 855-907; 
                 
                     
                   SEQ ID NO:01, nucl. 910-953; 
                 
                     
                   SEQ ID NO:01, nucl. 1007-1059; 
                 
                     
                   SEQ ID NO:01, nucl. 1147-1163; 
                 
                     
                   SEQ ID NO:01, nucl. 1258-1279; 
                 
                     
                   SEQ ID NO:01, nucl. 1375-1389; 
                 
                     
                   SEQ ID NO:01, nucl. 1581-1595; 
                 
                     
                   SEQ ID NO:01, nucl. 1621-1639; 
                 
                     
                   SEQ ID NO:01, nucl. 1744-1755; and 
                 
                     
                   SEQ ID NO:01, nucl. 1951-1969. 
                 
                     
                     
                 
                     
                     
                 
             
                
                
               
               
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         9 . A polynucleotide according to  claim 7 , comprising at least 72 contiguous nucleotides of a strand of SEQ ID NO:01.  
     
     
         10 . A polynucleotide according to  claim 7 , wherein the sequence is SEQ ID NO:13.  
     
     
         11 . A recombinant polynucleotide encoding a polypeptide according to  claim 1 .  
     
     
         12 . A cell comprising a polynucleotide according to  claim 11 .  
     
     
         13 . A method of making an R5.24 polypeptide, said method comprising steps: introducing a polynucleotide according to  claim 11  into a host cell or cellular extract, incubating said host cell or extract under conditions whereby said polynucleotide is expressed as a transcript and said transcript is expressed as a translation product comprising said polypeptide, and isolating said translation product.  
     
     
         14 . A method of screening for an agent which modulates the interaction of an R5.24 polypeptide to a binding target, said method comprising the steps of: 
 incubating a mixture comprising: 
 an isolated polypeptide according to  claim 1 ,  
 a binding target of said polypeptide, and  
 a candidate agent;  
   under conditions whereby, but for the presence of said agent, said polypeptide specifically binds said binding target at a reference affinity;    detecting the binding affinity of said polypeptide to said binding target to determine an agent-biased affinity, wherein a difference between the agent-biased affinity and the reference affinity indicates that said agent modulates the binding of said polypeptide to said binding target.    
     
     
         15 . A method according to  claim 14 , wherein the polypeptide is incorporated in a cell membrane and the binding affinity is detected by measuring ligand-binding mediated signal transduction through the polypeptide, across the membrane.  
     
     
         16 . A method of screening for a G protein-coupled receptor, said method comprising the steps of expression cloning using an expression system which detects activation of multiple signaling pathways by coexpressing at least one G protein selected from Gα olf  and Gs and at least one G protein-gated inwardly rectifying potassium channel, together with candidate receptors and identifying clones which yield agonist-dependent currents, wherein the receptor is an odorant receptor and the G protein is a Gα olf .