3/30/12

Protein knots



I have stumble upon the protein with a very interesting structural motif (PDB ID: 3UN9). Protein subunits forms functional receptor, subunits fit into each other like a pieces of a jigsaw puzzle.

Actually knots are not very rare  in protein kingdom. Take a look for example into databases like pKNOT or knot server from MIT. There is evidence that the artificial knot proteins can be  even successively designed (PDB ID: 3MLG) [1].

But one question arose looking at those type of structure: how this 3-to-1 or 6-to-1 proteins are folded? As it was found knot proteins do not require chaperons for folding, thus folding happens independently under influence of the internal and external conditions: protein itself and cell solution.  Mutations some of the amino acids directly involved in folding do not have great influence thus no "folding features" were found. Some of the knotted structures can be easily unfolded, but methyltransferase structures are very stable under   denaturing conditions. Also interesting to point out that the knots are forming on the late stages of the folding pathway [2].


Attempts to mimic folding in silico was successful [3]. Coarse-grained representation of the protein and simulation of Langevin dynamics for YibK  protein with trefoil knot have shown the early and late knot formation pathways. And as it was expected the hydrophobic aminoacids play the most important role.


One of the most important interests is design of artificial enzymes stable under very harsh conditions for industry.


References:
1. Structure and folding of a designed knotted protein - DOI: 10.1073/pnas.1007602107.
2. Nice review - DOI:10.1088/0953-8984/23/3/033101
3. Attempt to fold knot protein in silico: arxiv.org/abs/q-bio/0611073 













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