Award
National Cancer Institute 5F31CA295111-02
Deciphering APOBEC Inhibition: Unraveling Structural Dynamics via Viral Protein and Nanobody Interactions
Recipient
University of Minnesota
Award Amount
$35,827.00
Ceiling
$35,827.00
Awarded
June 24, 2026
Identifier
5F31CA295111-02
Research project to determine high-resolution structures of APOBEC3A and APOBEC3B enzymes bound to viral inhibitors and alpaca-derived nanobodies using cryo-EM, aiming to design inhibitors to reduce cancer mutagenesis and improve cancer treatment.
Description
This proposal focuses on elucidating the structural mechanisms of APOBEC3A (A3A) and APOBEC3B (A3B) inhibition using cryo-EM, employing viral antagonists (McHV-11 and KSHV RNRs) and novel alpaca-derived nanobodies. By determining high-resolution structures of A3A/B in complex with these inhibitors, this project aims to provide insights for the rational design of inhibitors to mitigate APOBEC-induced cancer mutagenesis. The innovative approach of integrating cryo-EM and engineered nanobodies represents a promising strategy for advancing precision medicine in cancer therapeutics.