Monobodies as enabling tools for structural and mechanistic biology.


Laura and Isaac Perlmutter Cancer Center, New York University Langone Health, 522 1st Avenue, New York, NY 10016, USA; Department of Medicine and Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, 522 1st Avenue, New York, NY 10016, USA. Electronic address: [Email]


Monobodies, built with the scaffold of the fibronectin type III domain, are among the most well-established synthetic binding proteins. They promote crystallization of challenging molecular systems. They have strong tendency to bind to functional sites and thus serve as drug-like molecules that perturb the biological functions of their targets. Monobodies lack disulfide bonds and thus they are particularly suited as genetically encoded reagents to be used intracellularly. This article reviews recent monobody-enabled studies that reveal new structures, molecular mechanisms and potential therapeutic opportunities. A systematic analysis of the crystal structures of monobody-target complexes suggests important attributes that make monobodies effective crystallization chaperones.