Abstract
Transcription activator-like effectors (TALEs) are DNA-related proteins that recognise and bind specific target sequences to manipulate gene expression. Recently determined crystal structures show that their common architecture reveals a superhelical overall structure that may undergo drastic conformational changes. To establish a link between structure and dynamics in TALE proteins we have employed coarse-grained elastic-network modelling of currently available structural data and implemented a force-probe setup that allowed us to investigate their mechanical behaviour in computer experiments. Based on the measured force-extension curves we conclude that TALEs exhibit superelastic dynamical properties allowing for large-scale global conformational changes along their helical axis, which represents the soft direction in such proteins. For moderate external forcing the TALE models behave like linear springs, obeying Hooke's law, and the investigated structures can be characterised and compared by a corresponding spring constant. We show that conformational flexibility underlying the large-scale motions is not homogeneously distributed over the TALE structure, but instead soft spot residues around which strain is accumulated and which turn out to represent key agents in the transmission of conformational motions are identified. They correspond to the RVD loop residues that have been experimentally determined to play an eminent role in the binding process of target DNA.
Highlights
TAL effectors are proteins that are secreted in plants by bacteria of the Xanthomonas genus
We considered the structures of two Transcription activator-like effectors (TALEs) proteins, that of the artificially engineered dHax3 in its DNA-free form (PDB ID 3V6P) and in a conformation determined in the presence of DNA (3V6T), and that of PthXo1 from the rice pathogen Xanthomonas oryzae which was co-crystallized with its DNA target (3UGM)
TALE structures the immobilised bead corresponded to residue Gly303 at the beginning of the 1b TALE repeat and the force was applied to the bead which corresponded to residue Gly675, which is located at the end of TALE repeat 12a
Summary
TAL (transcription activator-like) effectors are proteins that are secreted in plants by bacteria of the Xanthomonas genus. Upon injection into cells they are able to activate transcription of specific target plant genes which may be beneficial for bacterial infection [1,2]. The structure-function relationship of proteins, i.e. the principle of how the three dimensional folded protein conformation defines its functional activity, may reveal surprisingly simple patterns. In this regard molecular machines and motors represent a prime example. Their modular architecture, consisting of rigid domains connected by more flexible joints, gives rise to wellorganised relative internal motions through which the particular function is implemented [10,11]
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