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Supramolecular Motive Power

Final Report Summary - SUMO (Supramolecular Motive Power)

The objective of SUMO has been to increase understanding how energy in biological systems may translocate over nanometer-scale distance as mechanical deformation energy, in particular how such mechanisms drive fundamental biological processes. Such insight may also allow construction of bio-inspired supramolecular nanotechnical devices, including molecular motors. The achievements include: 1. Design of supramolecular DNA constructs and studies how DNA behaves while subject to external force, 2. Enzymes RecA and Rad51 that execute DNA strand exchange (genetic recombination), and 3. Theoretical studies on an enzyme (F1 ATP synthase) that can mechanically convert ADP to ATP.
1. In the first sub-project DNA, subject to external force using ”laser tweezers”, we report the discovery that single molecules of relatively short double-helical DNA sequences, rich in guanine-cytosine basepairs, undergo reversible extension into a new conformation: at 55 pico-Newton DNA undergoes a structural change into a 51% longer conformation which is still double-stranded, and when reducing the force the DNA immediately returns to its normal structure [1]. We postulate that the stretched conformation undergoes a disproportionation into triplets of stacked bases surrounded by empty gaps. Such a structure, which we early proposed based on observed perpendicularly stacked DNA bases in complex with RecA, may play a role in the search-for-homology of recombinases and might even be an origin of the genetic codon base-triplet. Finally, we anticipate these findings will also have impact for DNA-based supramolecular technology where the ERC project has meant progress in the synthesis of large 2-D networks that can be addressable using triple helix recognition strategy. This will allow bottom-up assembly of integrated functionalities that could be addressed and positioned on a surface (chip) at will [2].
2. Using polarized light (Linear Dichroism) spectroscopy DNA-protein complexes with the human recombinase Rad51 has been possible to resolve with respect to a 3-D structure model. The above mentioned inhomogeneous stretch of DNA fits that model and several interesting observations were made regarding how various cofactors affect the structure and function [3].
3. As for the F1 ATP synthase, this enzyme is of key importance for the energy balance of the cell: it can be run backwards and like a motor produce mechanical work when fed with ATP fuel. By quantum computations, combined with structure data and experimental kinetic results, we have developed an energetic model that can explain crucial steps in the catalytic mechanism of the enzyme, including relation to mechanical deformation and directionality of reaction [4].

1. N Bosaeus, AH El-Sagheer, T Brown, S B Smith, B Akerman, C Bustamante and B Nordén Tension Induces a Base-Paired Overstretched DNA Conformation Proc.Natl.Acad. Sci. (US) 109 (2012) 15179-15184.
2. E Lundberg, C Plesa, M Wilhelmsson, P Lincoln, T Brown and B Nordén Nano-fabrication yields. Hybridization and click- fixation of polycyclic DNA nano-assemblies American Chemical Society NANO. 5 (2011) 7565-7575.
3. Reymer A, Frykholm K, Morimatsu K, Takahashi M, Nordén B Structure of human Rad51 protein filament from molecular modeling and site-specific linear dichroism spectroscopy Proc.Nat.Ac.Sci. (USA) 106 (2009) 13248-13253; Louise H. Fornander, Karolin Frykholm, Anna Reymer, Axelle Renodon-Corniere, Masayuki Takahashi and Bengt Nordén Ca2+ improves organization of 
single-stranded DNA bases in human Rad51 filament, explaining stimulatory effect on gene recombination Nucl Acids Res. 40 (2012) 4904-4913.
4. T Beke Somfai, P Lincoln and B Nordén Rate of hydrolysis in ATP synthase is fine-tuned by a-subunit motif controlling active site conformation. Proc.Natl.Acad. Sci. (US) 110 (2013) 2117-2122.