BSB Seminar: Silently Shaping Structure – Probing for an association between codon usage and very local protein structure

Ailie Marx, Israel Institute of Technology

Abstract

One of the most fundamental assumptions in biology is that the amino acid sequence defines protein structure and that this sequence carries no memory of the specific mRNA codon sequence from which it was translated.  Challenging this assumption, we have recently shown, using codon-specific Ramachandran plots, that some synonymous codons (those translating into the same amino acid) are associated with different protein backbone dihedral angles around the encoded amino acid (Rosenberg, A., Marx, A., & Bronstein, A.M, 2022, Nature Communications).

Computationally, we are now refining our large-scale analysis of PDB available protein structures to identify regions free of spatial interactions and then using these “contact-free” regions to examine how differences in backbone conformation associate with coding.  We are also directly probing the causality of the codon – structure association by introducing computationally guided synonymous mutations into proteins for side by side functional and crystallographic experimental characterization to explore how synonymous coding affects local (and, subsequently, global) protein structure and the potential biological implications of this phenomenon.  

Biography

Ailie Marx is a researcher at the Department of Computer Science in the Technion – Israel Institute of Technology.  After completing a Bachelor of Science degree in the Australian National University she became interested in protein structure and X-ray crystallography. Ailie completed her PhD at the Technion, in the laboratory of Prof. Noam Adir, using high resolution crystal structures to piece together the enormous light harvesting Phycobilisome complex.  She went on to study host-virus interactions as a postdoctoral researcher with Prof. Akram Alian and later spent time in the Single Molecule Biophysics Laboratory headed by Prof. Ariel Kaplan.  Most recently Ailie has been working together with Prof. Alex Bronstein, employing computational analysis, molecular dynamics and crystallography to challenge one of the central dogmas of biology by asking if synonymous genetic coding can directly and specifically alter very local protein structure.