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dc.contributor.advisor Wagner, Daniel S.
dc.creatorRodriguez, Christopher Paul
dc.date.accessioned 2013-03-08T00:38:08Z
dc.date.available 2013-03-08T00:38:08Z
dc.date.issued 2012
dc.identifier.citation Rodriguez, Christopher Paul. "A library approach to single site and combinatorial residue contributions to dimerization of BNIP3-like transmembrane domains." (2012) Diss., Rice University. https://hdl.handle.net/1911/70413.
dc.identifier.urihttps://hdl.handle.net/1911/70413
dc.description.abstract A poly-leucine transmembrane domain library was randomized at positions corresponding to contact surfaces for a right-handed crossing of two helices to determine the significance of small residues, GxxxG motifs, and hydrogen bonding residues in driving helix-helix interactions within membranes. About 10000 sequences, which include the interfaces of tightly interacting biological transmembrane domains, were subjected to increasing selection strength in the membrane interaction assay TOXCAT and surviving clones were sequenced to identify single site and pairwise amino acid trends. Statistical analysis identified a central glycine to be essential to strong dimerization. The next strongest statistical preference was for a phenylalanine three positions before the key glycine. Secondary to these residues, polar histidine and asparagine residues are also favored in strongly dimerizing sequences, but not to the exclusion of hydrophobic leucine and isoleucine. The analysis identifies novel pairwise combinations that contribute to or are excluded from strong dimerization, the most striking of which is that the biologically important GxxxGxxxG/A pattern is under-represented in the most strongly associating BNIP3-like transmembrane dimers. The variety of residue combinations that support strong dimerization indicates that not only key 'motif' residues, but also the residues that flank them, are important for strong dimerization. Because favorable pairwise combinations of flanking residues occur between both proximal positions and residues separated by two or more turns of helix, the complexity of how sequence context influences motif-driven dimerization is very high.
dc.format.extent 162 p.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.subjectPure sciences
Biological sciences
Dimerization
Transmembrane domains
Combinatorial residue
Cellular biology
Microbiology
Biochemistry
dc.title A library approach to single site and combinatorial residue contributions to dimerization of BNIP3-like transmembrane domains
dc.identifier.digital RodriguezC
dc.type.genre Thesis
dc.type.material Text
thesis.degree.department Biochemistry and Cell Biology
thesis.degree.discipline Natural Sciences
thesis.degree.grantor Rice University
thesis.degree.level Doctoral
thesis.degree.name Doctor of Philosophy


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