Dissimilar flexibility of α and β subunits of human adult hemoglobin influences the protein dynamics and its alteration induced by allosteric effectors
| Autor: | Andras D. Kaposi, Judit Fidy, Levente Herényi, Gusztáv Schay, Krisztián Szigeti, László Smeller |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Luminescence lcsh:Medicine Plasma protein binding Molecular Dynamics Biochemistry Physical Chemistry 01 natural sciences Hemoglobins chemistry.chemical_compound Spectrum Analysis Techniques Computational Chemistry Protein structure Post-Translational Modification lcsh:Science Enzyme Chemistry Heme Multidisciplinary Physics Electromagnetic Radiation Protein dynamics Absorption Spectroscopy Chromophores Chemistry Physical Sciences Protein Binding Research Article Chemical Elements Protein subunit Allosteric regulation Molecular Dynamics Simulation Research and Analysis Methods 010402 general chemistry Fluorescence Enzyme Regulation 03 medical and health sciences Allosteric Regulation Humans Amino Acid Sequence Hemoglobin Protein Structure Quaternary Fluorescent Dyes Binding Sites lcsh:R Biology and Life Sciences Proteins 0104 chemical sciences Oxygen Protein Subunits Spectrometry Fluorescence 030104 developmental biology chemistry Enzymology Biophysics lcsh:Q Sequence Alignment Oxygen binding |
| Zdroj: | PLoS ONE PLoS ONE, Vol 13, Iss 3, p e0194994 (2018) |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0194994 |
| Popis: | The general question by what mechanism an "effector" molecule and the hemes of hemoglobin interact over widely separated intramolecular distances to change the oxygen affinity has been extensively investigated, and still has remained of central interest. In the present work we were interested in clarifying the general role of the protein matrix and its dynamics in the regulation of human adult hemoglobin (HbA). We used a spectroscopy approach that yields the compressibility (κ) of the protein matrix around the hemes of the subunits in HbA and studied how the binding of heterotropic allosteric effectors modify this parameter. κ is directly related to the variance of volume fluctuation, therefore it characterizes the molecular dynamics of the protein structure. For the experiments the heme groups either in the α or in the β subunits of HbA were replaced by fluorescent Zn-protoporphyrinIX, and series of fluorescence line narrowed spectra were measured at varied pressures. The evaluation of the spectra yielded the compressibility that showed significant dynamic asymmetry between the subunits: κ of the α subunit was 0.17±0.05/GPa, while for the β subunit it was much higher, 0.36±0.07/GPa. The heterotropic effectors, chloride ions, inositol hexaphosphate and bezafibrate did not cause significant changes in κ of the α subunits, while in the β subunits the effectors lead to a significant reduction down to 0.15±0.04/GPa. We relate our results to structural data, to results of recent functional studies and to those of molecular dynamics simulations, and find good agreements. The observed asymmetry in the flexibility suggests a distinct role of the subunits in the regulation of Hb that results in the observed changes of the oxygen binding capability. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|