NMR comparison of the native energy landscapes of DLC8 dimer and monomer

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 alternati...

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Bibliographic Details
Published in:Biophysical chemistry 2008-04, Vol.134 (1), p.10-19
Main Authors: Krishna Mohan, P.M., Barve, Maneesha, Chatterjee, Amarnath, Ghosh-Roy, Anindya, Hosur, Ramakrishna V.
Format: Article
Language:English
Subjects:
Amides - chemistry
Amino Acid Sequence
Conformational fluctuations
Dimerization
Dynein light chain protein
Dyneins - chemistry
Dyneins - metabolism
Energy landscape
Hydrogen-Ion Concentration
Low energy excited states
Magnetic Resonance Spectroscopy
Models, Molecular
Molecular Sequence Data
Nuclear magnetic resonance
Protein Binding
Protein Denaturation
Protein Structure, Quaternary
Protons
Sensitivity and Specificity
Temperature
Thermodynamics
Unfolding initiation sites
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Summary: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.
ISSN:0301-4622
1873-4200
DOI:10.1016/j.bpc.2007.12.010