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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

A library approach to single site and combinatorial residue contributions to dimerization of BNIP3-like transmembrane domains

January 2012 (has links)
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.

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