Dimeric structure of the transmembrane domain of glycophorin a in lipidic and detergent environments.
2011
Specific interactions between transmembrane α-helices, to a large extent, determine the biological function of integral membrane proteins upon normal development and in pathological states of an organism. Various membrane-like media, partially those mimicking the conditions of multicomponent biological mem- branes, are used to study the structural and thermodynamic features that define the character of oligomeriza- tion of transmembrane helical segments. The choice of the composition of the membrane-mimicking medium is conducted in an effort to obtain a biologically relevant conformation of the protein complex and a sample that would be stable enough to allow to perform a series of long-term experiments with its use. In the present work, heteronuclear NMR spectroscopy and molecular dynamics simulations were used to demonstrate that the two most widely used media (detergent DPC micelles and lipid DMPC/DHPC bicelles) enable to perform structural studies of the specific interactions between transmembrane α-helices by the example of dimerizing the trans- membrane domain of the bitopic protein glycophorin A. However, a number of peculiarities place lipid bicelles closer to natural lipid bilayers in terms of their physical properties. KEYWORDS bitopic membrane proteins; transmembrane domain; dimerization; spatial structure; molecular dy- namics; NMR ABBREVIATIONS ТМ - transmembrane; GpAtm - TM fragment 61-98 of human protein glycophorin A, GpA 61-98 ; DPC - dodecylphosphocholine; DMPC - dimyristoylphosphatidylcholine; DHPC - dihexanoylphosphatidyl - choline; RMSD - root-mean-square deviation; NOE - nuclear Overhauser effect; NOESY - nuclear Overhauser enhancement spectroscopy experiment; HSQC - heteronuclear single quantum coherence experiment
Keywords:
- Model lipid bilayer
- Transmembrane domain
- Nuclear magnetic resonance spectroscopy
- Heteronuclear single quantum coherence spectroscopy
- Transmembrane protein
- Membrane protein
- Biochemistry
- Integral membrane protein
- Two-dimensional nuclear magnetic resonance spectroscopy
- Biology
- Lipid bilayer
- Nuclear Overhauser effect
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