Significance of Knotted Structures for Function of Proteins and Nucleic Acids
Friday Abstracts
Mechanically Tightening a Protein Slipknot into a Trefoil Knot
Hongbin Li
1,2
.
1
University of British Columbia, Vancouver, Canada,
2
Tianjin University, Tianjin, China.
Knotted polypeptide chain is one of the most surprising topological features found in some
proteins. How knotted proteins overcome the topological difficulty to fold into their native three
dimensional structures proteins has become a challenging problem. It was suggested that a
structure of slipknot could serve as an important intermediate state during the folding of knotted
proteins. Here we use single molecule force spectroscopy (SMFS) as well as steered molecular
dynamics (SMD) simulations to investigate the mechanism of transforming a slipknot protein
AFV3-109 into a tightened trefoil knot by pulling. Our results show that by pulling the N-
terminus and the threaded loop of AFV3-109, the protein can be unfolded via multiple pathways
and the slipknot can be transformed into a tightened trefoil knot, which involves ~13 amino acid
residues. SMD simulation results, which are consistent with our experimental findings, provide a
detailed molecular mechanism of mechanical unfolding and knot tightening of AFV3-109. SMD
simulations reveal that interactions between β-strands on the threading loop and knotting loop
that are sheared during stretching provide high mechanical resistance in the process of forming
the trefoil knot, i.e., pulling threaded loop through knotting loop.
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