Katie Fitzgerald Rose Hills
Incorporating Unnatural Amino Acids via Mutant Ribosomes
The ribosome is conserved across biological organisms and is co-evolved with the genetic code to decode mRNA into proteins. Its macromolecular machinery is highly specific to the canonical set of twenty amino acids, leading to high fidelity yet low diversity of possible protein structure. Expanding the set of amino acids that can be successfully incorporated into proteins could lead to novel peptide structures and functions.
The Cate Lab aims to rationally engineer the ribosome to incorporate non-proteinogenic monomers. Cryogenic Electron Microscopy (Cryo-EM) has revealed A2062 as a possible site of steric clashes with bulkier amino acids within the ribosomal peptidyl transferase center (PTC). A mutation at A2062 could allow for incorporation of sterically hindered cyclic ꞵ-amino acids (cβAAs) into peptides. These particular amino acids contribute to the formation of foldamers, unique peptides with rigid secondary structures. Enhanced production of foldamers using cβAAs could lead to novel biopolymers and biopharmaceuticals.
Message To Sponsor
I deeply appreciate the opportunity to pursue a research project I care about this summer. I will be able to help advance knowledge of ribosomal structure and function, as well as develop independence and confidence in the research setting. I am looking forward to this summer and my future in the scientific community. Thank you so much!