Structural Disorder of the CD3 Transmembrane Domain Studied with 2D IR Spectroscopy and Molecular Dynamics Simulations
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- 作者：Prabuddha Mukherjee ; Itamar Kass ; Isaiah T. Arkin ; Martin T. Zanni
- 刊名：Journal of Physical Chemistry B
- 出版年：2006
- 出版时间：December 7, 2006
- 年：2006
- 卷：110
- 期：48
- 页码：24740 - 24749
- 全文大小：218K
- 年卷期：v.110,no.48(December 7, 2006)
- ISSN：1520-5207
文摘
In a recently reported study [Mukherjee, et al. Proc. Natl. Acad. Sci. U.S.A. 2006, 103, 3528], we used 2DIR spectroscopy and 1-13C=18O isotope labeling to measure the vibrational dynamics of 11 amide I modesin the CD3
transmembrane domain. We found that the homogeneous line widths and population relaxationtimes were all nearly identical, but that the amount of inhomogeneous broadening correlated with the positionof the amide group inside the membrane. In this study, we use molecular dynamics simulations to investigatethe structural and dynamical origins of these experimental observations. We use two models to convert thesimulations to frequency trajectories from which the mean frequencies, standard deviations, frequencycorrelation functions, and 2D IR spectra are calculated. Model 1 correlates the hydrogen-bond length to theamide I frequency, whereas model 2 uses an ab initio-based electrostatic model. We find that the structuraldistributions of the peptidic groups and their environment are reflected in the vibrational dynamics of theamide I modes. Environmental forces from the water and lipid headgroups partially denature the helices,shifting the infrared frequencies and creating larger inhomogeneous distributions for residues near the ends.The least inhomogeneously broadened residues are those located in the middle of the membrane whereenvironmental electrostatic forces are weakest and the helices are most ordered. Comparison of the simulationsto experiment confirms that the amide I modes near the C-terminal are larger than at the N-terminal becauseof the asymmetric structure of the peptide bundle in the membrane. The comparison also reveals that residuesat a kink in the 
-helices have broader line widths than more helical parts of the peptide because the peptidebackbone at the kink exhibits a larger amount of structural disorder. Taken together, the simulations andexperiments reveal that infrared line shapes are sensitive probes of membrane protein structural andenvironmental heterogeneity.
transmembrane domain. We found that the homogeneous line widths and population relaxationtimes were all nearly identical, but that the amount of inhomogeneous broadening correlated with the positionof the amide group inside the membrane. In this study, we use molecular dynamics simulations to investigatethe structural and dynamical origins of these experimental observations. We use two models to convert thesimulations to frequency trajectories from which the mean frequencies, standard deviations, frequencycorrelation functions, and 2D IR spectra are calculated. Model 1 correlates the hydrogen-bond length to theamide I frequency, whereas model 2 uses an ab initio-based electrostatic model. We find that the structuraldistributions of the peptidic groups and their environment are reflected in the vibrational dynamics of theamide I modes. Environmental forces from the water and lipid headgroups partially denature the helices,shifting the infrared frequencies and creating larger inhomogeneous distributions for residues near the ends.The least inhomogeneously broadened residues are those located in the middle of the membrane whereenvironmental electrostatic forces are weakest and the helices are most ordered. Comparison of the simulationsto experiment confirms that the amide I modes near the C-terminal are larger than at the N-terminal becauseof the asymmetric structure of the peptide bundle in the membrane. The comparison also reveals that residuesat a kink in the -helices have broader line widths than more helical parts of the peptide because the peptidebackbone at the kink exhibits a larger amount of structural disorder. Taken together, the simulations andexperiments reveal that infrared line shapes are sensitive probes of membrane protein structural andenvironmental heterogeneity.