title: NMR comparison of the native energy landscapes of DLC8 dimer and monomer.
abstract: Characterization of the low energy excited states on the energy landscape of a protein is one of the exciting and challenging problems in structural biology today. In this context, we present here residue level NMR description of the low energy excited states representing locally different alternative conformations in the dynein light chain protein, in its dimeric as well as monomeric forms. Important differences have been observed between the two cases and these are not necessarily restricted to the dimer interface. Simulations indicate that the low energy excited states are within a free energy of 2-3 kcal/mol above the native state. In both the monomer and the dimer the energy landscape is very sensitive to small pH perturbations. Nearly 25% of the residues (total of residues at pH 3.0 and 3.5 for the monomer, and at pH 7.0 and 6.0 for the dimer) access alternative conformations. The observations have been rationalized on the basis of protonation-deprotonation equilibria in the side chains; histidines in the case of the dimer and aspartates/glutamates in the case of the monomer. The possible relationship of the observed ruggedness of the native energy landscape with the protein structure, and its implications to protein adaptability and unfolding have been discussed.
authors.affiliation: Department of Chemical Sciences, Tata Institute of Fundamental Research, Homi Bhabha Road, Mumbai 400 005, India.
authors.forename: P M
authors.initials: PM
authors.lastname: Krishna Mohan
authors.forename: Maneesha
authors.initials: M
authors.lastname: Barve
authors.forename: Amarnath
authors.initials: A
authors.lastname: Chatterjee
authors.forename: Anindya
authors.initials: A
authors.lastname: Ghosh-Roy
authors.forename: Ramakrishna V
authors.initials: RV
authors.lastname: Hosur
mesh_terms: D000577:Amides / Q000737:chemistry; D000595:Amino Acid Sequence; D019281:Dimerization; D004398:Dyneins / Q000737:chemistry* / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D011489:Protein Denaturation; D020836:Protein Structure, Quaternary; D011522:Protons; D012680:Sensitivity and Specificity; D013696:Temperature; D013816:Thermodynamics
chemical_list: D000577:Amides; D011522:Protons; D004398:Dyneins