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    The Influence of Hydrophobic Mismatch on Structure and Dynamics of Transmembrane Helices and Lipid Bilayers

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    Issue Date
    2011-12-31
    Author
    Kim, Taehoon
    Publisher
    University of Kansas
    Format
    187 pages
    Type
    Dissertation
    Degree Level
    Ph.D.
    Discipline
    Biochemistry & Molecular Biology
    Rights
    This item is protected by copyright and unless otherwise specified the copyright of this thesis/dissertation is held by the author.
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    Abstract
    Membrane proteins with one or a few transmembrane (TM) helices are abundant and often involved in important TM-included signaling and regulation through formation of hetero- and homo-oligomers. Especially, solid-state NMR (SSNMR) is a powerful technique to describe the orientations of membrane proteins and peptides in their native membrane bilayer environments. However, it is still challenging to obtain the structural information of membrane protein. Since protein-lipid interaction and bilayer regulation of membrane protein functions are largely controlled by the hydrophobic match between the TM domain of membrane proteins and the surrounding lipid bilayer, the interplay between the structure and the energetics of lipid and protein components of biomembranes is one of long-standing interests in biophysics. Structural and dynamic changes of the TM helices in response to a hydrophobic mismatch as well as molecular forces governing such changes remain to be fully understood at the atomic level. In this dissertation, to systematically characterize responses of a TM helix and lipid adaptations to a hydrophobic mismatch, I have performed a total of 5.8-μs umbrella sampling simulations and calculated the potentials of mean force (PMFs) as a function of TM helix tilt angle under various mismatch conditions. Single-pass TM peptides called WALP were used in two lipid bilayers with different hydrophobic thicknesses to consider hydrophobic mismatch caused by either the TM length or the bilayer thickness. The deuterium (2H) quadrupolar splitting (DQS), one of the SSNMR observables, has been used to characterize the orientations of various single-pass TM helices using a semi-static rigid-body model such as the geometric analysis of labeled alanine (GALA) method. However, dynamic information of these TM helices, which could be related to important biological function, can be missing or misinterpreted with the semi-static model. The result in Chapter 3 demonstrates that SSNMR ensemble dynamics provides a means to extract orientational and dynamic information of TM helices from their SSNMR observables and to explain the discrepancy between molecular dynamics simulation and GALA-based interpretation of DQS data. Finally, this dissertation describes the influence of hydrophobic mismatch on structure and dynamics of TM helices and lipid bilayers through molecular dynamics simulation of Gramicidin A (gA) channel in various lipid bilayers. The structure and dynamics of the gA channel as well as important lipid properties were investigated to address the influence by various hydrophobic mismatch conditions.
    URI
    http://hdl.handle.net/1808/9753
    Collections
    • Dissertations [4475]
    • Molecular Biosciences Dissertations and Theses [270]

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    785-864-8983
    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
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    Contact KU ScholarWorks
    785-864-8983
    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    Image Credits
     

     

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