Structural and biophysical studies of HIV-1 Rev protein

dc.contributor.advisorRobert O. Fox, Ph.D.en_US
dc.contributor.committeeMemberVince J. Hilser, Ph.D.en_US
dc.contributor.committeeMemberSusan Marriott, Ph.D.en_US
dc.contributor.committeeMemberMiles W. Cloyd, Ph.D.en_US
dc.contributor.committeeMemberEdmund W. Czerwinski, Ph.D.en_US
dc.creatorYe Pengen_US
dc.date.accessioned2011-12-20T16:04:27Z
dc.date.available2010-09-28en_US
dc.date.available2011-12-20T16:04:27Z
dc.date.created2006-03-29en_US
dc.date.issued2006-03-20en_US
dc.description.abstractRev is a key HIV-1 virus regulatory protein, which exports the unspliced and partially\r\nspliced viral mRNA out of the nucleus, thereby inducing the switch from the early phase\r\nto the late phase of the viral replication cycle. Because it is prone to form filaments at\r\nvery low concentration, the X-ray crystallography or NMR approaches to solving Rev\r\nstructure are very difficult. In my dissertation studies, I have designed several structural\r\nmutants of Rev. Under physiological conditions, I found RevC mutant behaves as a\r\nnatively unfolded monomer in solution. The segmentally disordered character of RevC\r\nwas supported by CD and HSQC studies. Another structural Rev mutant is the Rev loop\r\ndeletion. I used a Gly-Ser-Gly-Ala linker to take the place of the Rev loop and most of\r\nthe Arg-rich domain. This mutant can stay in solution as oligomers in sub-millimolar\r\nconcentration for NMR studies. The HSQC spectra of the Rev loop deletion and the\r\nRevC can be well overlaid except the HSQC of Rev loop deletion which has less peaks\r\nunder the same threshold. It brings a filament model with a thin wall formed by Rev Nterminal\r\ntwo helixes and a flexible Rev C-terminal freely moving inside. The flexible\r\ncharacter of Rev C-terminal is also proved to be true for the Rev wild type in comparing\r\nthe HSQC of Rev wild type and RevC. The HSQC of Rev wild type was obtained from\r\n15N labeled Rev and 132B23 complex. B23 is a major cellular component which binds\r\nRev. I designed an N-terminal core of B23, 132B23, and found that it binds with Rev and\r\nforms a decamer with Rev and 132B23 heterodimer.en_US
dc.format.mediumelectronicen_US
dc.identifier.otheretd-03292006-105724en_US
dc.identifier.urihttp://hdl.handle.net/2152.3/70
dc.language.isoengen_US
dc.rightsCopyright © is held by the author. Presentation of this material on the TDL web site by The University of Texas Medical Branch at Galveston was made possible under a limited license grant from the author who has retained all copyrights in the works.en_US
dc.subjectReven_US
dc.subjectHIV-1en_US
dc.subjectB23en_US
dc.titleStructural and biophysical studies of HIV-1 Rev proteinen_US
dc.type.genredissertationen_US
dc.type.materialtexten_US
thesis.degree.departmentBiochemistry and Molecular Biologyen_US
thesis.degree.grantorThe University of Texas Medical Branchen_US
thesis.degree.levelDoctoralen_US
thesis.degree.namePhDen_US

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