Structural and Motional Contributions of the Bacillus subtilis ClpC N-Domain to Adaptor Protein Interactions
Kojetin, D. J., McLaughlin, P. D., Thompson, R. J., Dubnau, D., Prepiak, P., Rance, M., & Cavanagh, J. (2009). Structural and Motional Contributions of the Bacillus subtilis ClpC N-Domain to Adaptor Protein Interactions. Journal of Molecular Biology, 387(3), 639-652. DOI: 10.1016/j.jmb.2009.01.046
The AAA(+) (ATPases associated with a variety of cellular activities) superfamily protein ClpC is a key regulator of cell development in Bacillus subtilis. As part of a large oligomeric complex, ClpC controls an array of cellular processes by recognizing, unfolding, and providing misfolded and aggregated proteins as substrates for the ClpP peptidase. ClpC is unique compared to other HSP100/Clp proteins, as it requires an adaptor protein for all fundamental activities. The NMR solution structure of the N-terminal repeat domain of ClpC (N-ClpCR) comprises two structural repeats of a four-helix motif. NMR experiments used to map the MecA adaptor protein interaction surface of N-ClpCR reveal that regions involved in the interaction possess conformational flexibility and conformational exchange on the microsecond-to-millisecond timescale. The electrostatic surface of N-ClpCR differs substantially from the N-domain of Escherichia coli ClpA and ClpB, suggesting that the electrostatic surface characteristics of HSP100/Clp N-domains may play a role in adaptor protein and substrate interaction specificity, and perhaps contribute to the unique adaptor protein requirement of ClpC.