Structural Survey of Select Spectrin Type Repeats within the Rod Region of Dystrophin Using Hydrophobic Moment Analysis and Molecular Dynamics Supplementing Crystallographic Data

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Description

Dystrophin is a rod shaped protein consisting of amino- and carboxy-terminal binding domains linked by a large central rod composed of 24 homologous copies of the STR motif and 5 non-homologous regions termed hinges. There are no high-resolution crystallographic structures available for the STR... Show moreDystrophin is a rod shaped protein consisting of amino- and carboxy-terminal binding domains linked by a large central rod composed of 24 homologous copies of the STR motif and 5 non-homologous regions termed hinges. There are no high-resolution crystallographic structures available for the STR repeats. This work yielded protein crystals and data sets of two STR fragments (d5 & d16-17). Though unable to produce a high resolution structure, this work examines the physical properties of the rod region utilizing hydrophobic moment analysis and molecular dynamics to suggest flexibility among the helices of the STR fragments. Helical shifting appears to possibly occur among the more stable STR tandems to increase the cooperation among certain adjacent fragments. A full understanding of how these properties vary along the length of the rod has implications for the engineering of these rods regions in future dystrophin therapies.
Ph.D. in Biology, July 2012 Show less

Details
Department

BIOL / Biology

Title

Structural Survey of Select Spectrin Type Repeats within the Rod Region of Dystrophin Using Hydrophobic Moment Analysis and Molecular Dynamics Supplementing Crystallographic Data

Institution

Illinois Institute of Technology

Creator(s)

Reinfelds, Pauls Edvins

Advisor(s)

Howard, Andrew

Date

2012-07-18
2012-07

Description

Dystrophin is a rod shaped protein consisting of amino- and carboxy-terminal binding domains linked by a large central rod composed of 24 homologous copies of the STR motif and 5 non-homologous... Show moreDystrophin is a rod shaped protein consisting of amino- and carboxy-terminal binding domains linked by a large central rod composed of 24 homologous copies of the STR motif and 5 non-homologous regions termed hinges. There are no high-resolution crystallographic structures available for the STR repeats. This work yielded protein crystals and data sets of two STR fragments (d5 & d16-17). Though unable to produce a high resolution structure, this work examines the physical properties of the rod region utilizing hydrophobic moment analysis and molecular dynamics to suggest flexibility among the helices of the STR fragments. Helical shifting appears to possibly occur among the more stable STR tandems to increase the cooperation among certain adjacent fragments. A full understanding of how these properties vary along the length of the rod has implications for the engineering of these rods regions in future dystrophin therapies. Show less

Type

Dissertation

File type

application/pdf

Access

Restricted Access

Rights

In Copyright
http://rightsstatements.org/page/InC/1.0/

Identifier

http://hdl.handle.net/10560/2934

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