Nickel-responsive protein NikR regulates the nickel uptake in nickel-dependent bacteria by interacting with the operator of nikABCDE and subsequently repressing the transcription of NikABCDE, an ABC-type nickel transporter system. The function of NikR and its affinity for the operator DNA is highly conformation-dependent, which has been confirmed by three independent crystallographic studies on NikR proteins from different bacteria. Depending on the intracellular nickel concentration, NikR is able to adopt either the open form or one of the two closed forms (cis and trans) that differ in the domain-domain arrangement. Only the closed cis form is optimal for DNA binding. We examined the low-resolution vibrational spectrum of NikR in each conformational form using the elastic network model and observed large-scale domain-domain vibrations that are closely related to the conformational transitions required for function, particularly the symmetric bending mode and the asymmetric twisting mode. This analysis on the intrinsic dynamics coded in the three-dimensional molecular construct allows us to examine the proposed mechanisms of NikR regulation from the standpoint of protein collective motions. Our findings further support the three-state equilibrium hypothesis proposed by others, and imply that an isolated closed cis form may be dynamically unstable but can be stabilized by DNA binding. However, we also found that the simple Cα-model used in the current analysis is insufficient to capture the impact of nickel binding on the protein dynamics, for which an all-atom model with detailed atom typing is more appropriate
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