title: pH driven conformational dynamics and dimer-to-monomer transition in DLC8.
abstract: Dynein light chain protein, a part of the cytoplasmic motor assembly, is a homodimer at physiological pH and dissociates below pH 4.5 to a monomer. The dimer binds to a variety of cargo, whereas the monomer does not bind any of the target proteins. We report here the pH induced stepwise structural and motional changes in the protein, as derived from line broadening and 15N transverse relaxation measurements. At pH 7 and below until 5, partial protonation and consequent interconversion between molecules carrying protonated and neutral histidines, causes conformational dynamics in the dimeric protein and this increases with decreasing pH. Enhanced dynamics in turn leads to partial loosening of the structure. This would have implications for different efficacies of binding by target proteins due to small variations in pH in different parts of the cell, and hence for cargo trafficking from one part to another. Below pH 5, enhanced charge repulsions, partial loss of hydrophobic interactions, and destabilization of H-bonds across the dimer interface cause further loosening of the dimeric structure, leading eventually to the dissociation of the dimer.
authors.affiliation: Department of Chemical Sciences, Tata Institute of Fundamental Research, Homi Bhabha Road, Mumbai 400 005, India.
authors.forename: P M Krishna
authors.initials: PM
authors.lastname: Mohan
authors.forename: Maneesha
authors.initials: M
authors.lastname: Barve
authors.forename: Amarnath
authors.initials: A
authors.lastname: Chatterjee
authors.forename: Ramakrishna V
authors.initials: RV
authors.lastname: Hosur
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D019281:Dimerization; D029721:Drosophila Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000378:metabolism; D004398:Dyneins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy; D011485:Protein Binding; D011487:Protein Conformation; D011522:Protons
chemical_list: D002352:Carrier Proteins; D029721:Drosophila Proteins; D011522:Protons; D004398:Dyneins