Multispecific recognition: Mechanism, evolution, and design

Ariel Erijman, Yonatan Aizner, Julia M. Shifman

Research output: Contribution to journalArticlepeer-review

47 Scopus citations


Accumulating evidence shows that many particular proteins have evolved to bind multiple targets, including other proteins, peptides,DNA, and smallmolecule substrates.Multispecific recognitionmight be not only common but also necessary for the robustness of signaling and metabolic networks in the cell. It is also important for the immune response and for regulation of transcription and translation.Multispecificity presents an apparent paradox: How can a protein encoded by a single sequence accommodate numerous targets? Analysis of sequences and structures of multispecific proteins revealed a number of mechanisms that achieve multispecificity. Interestingly, similar mechanisms appear in antibody-antigen, T-cell receptor-peptide, protein-DNA, enzyme-substrate, and protein-protein complexes. Directed evolution and protein design experiments with multispecific proteins offer some interesting insights into the evolution of such proteins and help in the dissection of molecular interactions that mediate multispecificity. Understanding the basic principles governing multispecificity could greatly assist in the unraveling of various complex processes in the cell. In addition, through manipulation of functional multispecificity, novel proteins could be created for use in various biotechnological and biomedical applications.

Original languageAmerican English
Pages (from-to)602-611
Number of pages10
Issue number5
StatePublished - 8 Feb 2011


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