Engineered heterodimeric protein domains

Abstract

The present invention provides an engineered multidomain protein including at least two nonidentical engineered domains, each of which contains a protein-protein interaction interface containing amino acid sequence segments derived from two or more existing homologous parent domains, thereby conferring on the engineered domains assembly specificities distinct from assembly specificities of the parent domains. In particular, the engineered domains form heterodimers with one another preferentially over forming homodimers. Methods of designing and using the engineered proteins are also included.

What is claimed is: 
     
         1 - 16 . (canceled) 
     
     
         17 . A method of colocalizing bio-active domains when administered to a biological system, the method comprising the step of administering to the biological system a multimeric protein comprising at least first and second nonidentical engineered domains, each of the first and second engineered domains containing a protein-protein interaction interface comprising amino acid sequence segments derived from two or more naturally occurring homologous parent domains, thereby conferring on said first and second engineered domains assembly specificities distinct from assembly specificities of the parent domains, wherein the first and second engineered domains form heterodimers with one another preferentially over forming homodimers, wherein the multidomain protein comprises a first bio-active domain comprising an antibody variable domain, and wherein the multidomain protein further comprises a second bio-active domain comprising a second antibody variable domain with distinct specificity. 
     
     
         18 . The method of  claim 17 , wherein the biological system is a mammal. 
     
     
         19 - 35 . (canceled)