Conformational and topological protein regulation

Abstract

Methods and compositions are provided for identifying novel conformers of proteins not known to exist as different conformers. By using chimeric genes replacing a native signal sequence with a different signal sequence resulting in the production of a conformer, one can compare the native protein with the product of the chimeric gene. Where the conformations are different, the different protein may be used for production of antibodies, elucidation of mechanisms associated with the native and different conformer protein, assays for the presence of the different conformer in physiological samples, identification of compounds specifically binding to the conformer, particularly drugs, etc. Where the formation of the conformer is associated with a diseased state, the conformer may be used in screens to identify compounds as drug candidates.

1 - 16 . (canceled)  
     
     
         17 . A method for identifying the presence of a conformer in a sample, said method comprising; 
 combining said sample with an antibody that binds to a wild-type protein; and    detecting the altered binding of said antibody, wherein altered binding of one or more protein in said sample to said antibody as compared to binding of said antibody to said wild-type protein is an indication of the presence of one or more conformer of said wild-type protein in said sample.    
     
     
         18 - 55 . (canceled)  
     
     
         56 . The method according to  claim 17 , wherein said antibody has a higher affinity for said conformer than for said wild-type protein  
     
     
         57 . The method according to  claim 17 , wherein said antibody is a monoclonal antibody.