Dynamic allostery of protein alpha helical coiled-coils.
Alpha helical coiled-coils appear in many important allosteric proteins such as the dynein molecular motor and bacteria chemotaxis transmembrane receptors. As a mechanism for transmitting the information of ligand binding to a distant site across an allosteric protein, an alternative to conformational change in the mean static structure is an induced change in the pattern of the internal dynamics of the protein. We explore how ligand binding may change the intramolecular vibrational free energy of a coiled-coil, using parameterized coarse-grained models, treating the case of dynein in detail. The models predict that coupling of slide, bend and twist modes of the coiled-coil transmits an allosteric free energy of approximately 2kBT, consistent with experimental results. A further prediction is a quantitative increase in the effective stiffness of the coiled-coil without any change in inherent flexibility of the individual helices. The model provides a possible and experimentally testable mechanism for transmission of information through the alpha helical coiled-coil of dynein.
Hawkins
Rhoda J
RJ
School of Physics and Astronomy, and Astbury Centre for Structural Molecular Biology, University of Leeds, IRC in Polymer Science and Technology, Leeds, LS2 9JT, UK. rhoda.hawkins@physics.org
McLeish
Tom C B
TC
D001665:Binding Sites; D003198:Computer Simulation; D004398:Dyneins / Q000737:chemistry* / Q000648:ultrastructure; D004735:Energy Transfer; D007536:Isomerism; D007700:Kinetics; D008870:Microtubules / Q000737:chemistry* / Q000648:ultrastructure; D008956:Models, Chemical; D008958:Models, Molecular; D020409:Molecular Motor Proteins / Q000737:chemistry*; D009038:Motion; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary
D020409:Molecular Motor Proteins; D004398:Dyneins