סמינר לפיזיקה של מערכות ביולוגיות וחומרים רכים: A TWIST in the protein folding dogma: Understanding how codon usage can create different protein structures from the same amino acid sequence

Abstract:

The fact that some amino acid chains fold alone into natively structured and fully functional proteins in solution, has led to the commonly accepted “one sequence-one structure” notion. However, within the cell, protein chains are not formed in isolation, to fold alone once produced.  Rather, they are translated from genetic coding instructions (for which many versions exist to code a single amino acid sequence) and begin to fold before the chain has fully formed through a process known as co-translational folding.  The effect of coding and co-translational folding mechanisms on the final protein structure are not well understood and there are no studies showing side by side structural analysis of protein pairs having alternative synonymous coding. We are using the wealth of high resolution protein structures available in the Protein Data Bank to computationally explore the association between genetic coding and local protein structure and pinpoint positions of alternate conformations in homologous proteins which cannot be readily explained by the amino acid sequence or protein environment.