Broad disorder and the allosteric mechanism of myosin II regulation by phosphorylation

Autor: Jean Chamoun, Likai Song, Paul J. Brewer, Christine R. Cremo, Piotr G. Fajer, Brian D. Haldeman, Bridget Salzameda, Hua Liang, Hui-Chun Li, Kevin C. Facemyer, Bertrand Vileno
Přispěvatelé: Swiss Federal Institute of Technology (EPFL), National Physical Laboratory [Teddington] (NPL), University of Warwick [Coventry], Institute of Precision Optical Engineering [Shangai] (IPOE), Tongji University
Rok vydání: 2011
Předmět:
Myosin Light Chains
Myosin light-chain kinase
Protein Conformation
Stereochemistry
Allosteric regulation
macromolecular substances
[CHIM.INOR]Chemical Sciences/Inorganic chemistry
010402 general chemistry
01 natural sciences
03 medical and health sciences
Myosin head
chemistry.chemical_compound
Adenosine Triphosphate
Protein structure
Allosteric Regulation
Myosin
Animals
[SDV.IMM.ALL]Life Sciences [q-bio]/Immunology/Allergology
Phosphorylation
Smooth Muscle Myosins
ComputingMilieux_MISCELLANEOUS
030304 developmental biology
Myosin Type II
0303 health sciences
Multidisciplinary
Heavy meromyosin
Chemistry
Electron Spin Resonance Spectroscopy
[CHIM.MATE]Chemical Sciences/Material chemistry
Biological Sciences
0104 chemical sciences
[SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry
Molecular Biology/Biophysics
Biophysics
Spin Labels
[PHYS.PHYS.PHYS-CHEM-PH]Physics [physics]/Physics [physics]/Chemical Physics [physics.chem-ph]
Chickens
Adenosine triphosphate
Zdroj: Proceedings of the National Academy of Sciences of the United States of America
Proceedings of the National Academy of Sciences of the United States of America, National Academy of Sciences, 2011, 108 (20), pp.8218-8223. ⟨10.1073/pnas.1014137108⟩
ISSN: 1091-6490
0027-8424
DOI: 10.1073/pnas.1014137108
Popis: Double electron electron resonance EPR methods was used to measure the effects of the allosteric modulators, phosphorylation, and ATP, on the distances and distance distributions between the two regulatory light chain of myosin (RLC). Three different states of smooth muscle myosin (SMM) were studied: monomers, the short-tailed subfragment heavy meromyosin, and SMM filaments. We reconstituted myosin with nine single cysteine spin-labeled RLC. For all mutants we found a broad distribution of distances that could not be explained by spin-label rotamer diversity. For SMM and heavy meromyosin, several sites showed two heterogeneous populations in the unphosphorylated samples, whereas only one was observed after phosphorylation. The data were consistent with the presence of two coexisting heterogeneous populations of structures in the unphosphorylated samples. The two populations were attributed to an on and off state by comparing data from unphosphorylated and phosphorylated samples. Models of these two states were generated using a rigid body docking approach derived from EM [Wendt T, Taylor D, Trybus KM, Taylor K (2001) Proc Natl Acad Sci USA 98:4361–4366] (PNAS, 2001, 98:4361–4366), but our data revealed a new feature of the off-state, which is heterogeneity in the orientation of the two RLC. Our average off-state structure was very similar to the Wendt model reveal a new feature of the off state, which is heterogeneity in the orientations of the two RLC. As found previously in the EM study, our on-state structure was completely different from the off-state structure. The heads are splayed out and there is even more heterogeneity in the orientations of the two RLC.
Databáze: OpenAIRE
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