title: Membrane-induced changes in the holomyoglobin tertiary structure: interplay with function.
abstract: The effect of anionic phospholipid membranes on holomyoglobin (holoMb) conformation and deoxygenation was studied. HoloMb structural changes and behavior in the presence of membranes were monitored by a variety of techniques including far UV and near UV circular dichroism, tryptophan (Trp) fluorescence, absorbance in the Soret region, differential scanning calorimetry, (1)H-NMR spectroscopy, size exclusion chromatography, and macroscopic diffusion. Kinetics of deoxygenation was monitored by absorption at 581 nm. The results gave evidence that proximity to a negatively charged membrane surface can cause destabilization of the structure of holomyoglobin, which delivers oxygen (O2) to mitochondria. It was shown that holoMb undergoes the native-to-intermediate-state transition in the presence of anionic phospholipid membranes at neutral pH, and that in this state it is able to interact with the membranes. When in the intermediate state, holoMb loses its rigid tertiary structure but preserves a pronounced secondary one. The presence of anionic phospholipid membranes substantially accelerates the process of deoxygenation. A possible functional role of the more flexible protein structure acquired in immediate proximity to the membrane surface is discussed.
authors.affiliation: Institute of Protein Research, Russian Academy of Sciences, 4 Institutskaya St., Pushchino, Moscow Region, 142290, Russian Federation.
authors.forename: Liana V
authors.initials: LV
authors.lastname: Basova
authors.forename: Elisaveta I
authors.initials: EI
authors.lastname: Tiktopulo
authors.forename: Victor P
authors.initials: VP
authors.lastname: Kutyshenko
authors.forename: Stanislav I
authors.initials: SI
authors.lastname: Klenin
authors.forename: Vitalii A
authors.initials: VA
authors.lastname: Balobanov
authors.forename: Valentina E
authors.initials: VE
authors.lastname: Bychkova
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000737:chemistry* / Q000378:metabolism*; D006418:Heme / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D009211:Myoglobin / Q000737:chemistry* / Q000378:metabolism*; D009994:Osmolar Concentration; D010100:Oxygen / Q000378:metabolism; D010743:Phospholipids / Q000494:pharmacology; D017434:Protein Structure, Tertiary / Q000187:drug effects
chemical_list: D009211:Myoglobin; D010743:Phospholipids; D006418:Heme; D010100:Oxygen