Abstract: This disclosure describes non-naturally occurring protein scaffolds and methods of making and using the protein scaffolds. In one aspect, therefore, this disclosure describes a non-naturally occurring protein scaffold that includes a plurality of structural domains and a plurality of loop regions that include an amino acid sequence that varies from a naturally-occurring loop region by at least one amino acid deletion, substitution, or addition. Generally, the structural domain or domains can include at least one ? structure and/or at least one a helix.

Abstract: This disclosure describes a non-naturally occurring protein scaffold that specifically binds to hepatocyte growth factor receptor (MET) and methods of using such protein scaffolds. Generally, the protein scaffold includes a frame and at least one loop region that specifically binds hepatocyte growth factor receptor (MET). The frame generally includes a plurality of structural domains that include at least one ? structure or at least one ? helix. The loop region generally includes an amino acid sequence that varies from a naturally-occurring loop region by at least one amino acid deletion, amino acid substitution, or amino acid addition.

Abstract: This disclosure describes a non-naturally occurring protein scaffold that specifically binds to hepatocyte growth factor receptor (MET) and methods of using such protein scaffolds. Generally, the protein scaffold includes a frame and at least one loop region that specifically binds hepatocyte growth factor receptor (MET). The frame generally includes a plurality of structural domains that include at least one ? structure or at least one a helix. The loop region generally includes an amino acid sequence that varies from a naturally-occurring loop region by at least one amino acid deletion, amino acid substitution, or amino acid addition.

Abstract: This disclosure describes non-naturally occurring protein scaffolds and methods of making and using the protein scaffolds. In one aspect, therefore, this disclosure describes a non-naturally occurring protein scaffold that includes a plurality of structural domains and a plurality of loop regions that include an amino acid sequence that varies from a naturally-occurring loop region by at least one amino acid deletion, substitution, or addition. Generally, the structural domain or domains can include at least one ? structure and/or at least one a helix.

Abstract: The present invention features engineered proteins that can include a genetically modified Fn domain; two or more such domains joined to one another; or at least one genetically modified Fn domain joined to a target-specific protein scaffold. One or more accessory sequences can be included in or added to any of these configurations. Methods of use, including methods of treating cancer, with the engineered proteins are also disclosed.