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dc.contributor.advisor MacKenzie, Kevin R.
dc.creatorDews, Ian Charles
dc.date.accessioned 2009-06-03T19:53:04Z
dc.date.available 2009-06-03T19:53:04Z
dc.date.issued 2008
dc.identifier.urihttps://hdl.handle.net/1911/22270
dc.description.abstract Protein-protein interactions between the transmembrane domains (TMDs) of integral membrane proteins have been increasingly implicated in contributing to biological function. In this thesis, I explore the strength, specificity and sequence dependence of interactions made by the TMDs of the syndecans, a family of four human cell adhesion molecules. Primary sequence alignment of all known syndecan TMDs reveals a completely conserved GxxxG dimerization motif. This motif has been shown to drive dimerization of many biological TMDs, and its strong conservation within the syndecan family would seem to suggest that all syndecans will display a common self-association phenotype. In contrast to this expectation, I show that the syndecan TMDs display a hierarchy of association phenotypes, with the syndecan-1 TMD showing very weak dimerization, the syndecan-3 and -4 TMDs showing strong dimerization, and the syndecan-2 TMD showing very strong dimerization. I further show that oligomerization of the syndecan TMDs depends upon the sequence element GxxxGxxxA, which is also conserved across all known syndecans. Using single and double point mutations, show that residue identities at two positions flanking the GxxxGxxxA motif combine to produce much of the difference in self-association strengths across syndecan paralogs. Residue identities at these intervening positions are different between paralogs but strongly conserved across orthologs, indicating an evolutionary pressure to maintain the hierarchy of association phenotypes. I further show that each syndecan TMD is capable of forming heteromeric complexes with at least two other paralogs and that these interactions are also supported by the GxxxG motif. The strength and stoichiometry of the heteromeric interactions are also paralog specific, meaning that residues in addition to the GxxxG motif are responsible for directing these interactions. These findings show that, although all syndecans possess a GxxxGxxxA sequence element that supports oligomerization, additional residues modulate the strength and stoichiometry of both homo- and heterotypic interactions. The strong conservation of residues that give rise to paralog specific homo- and heterotypic interactions suggests that the complexity of these interactions may play a role in mediating syndecan functions.
dc.format.extent 102 p.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.subjectMolecular biology
Cell biology
dc.title Characterization of transmembrane domain interactions by the syndecan family of integral membrane proteins
dc.type.genre Thesis
dc.type.material Text
thesis.degree.department Biology
thesis.degree.discipline Natural Sciences
thesis.degree.grantor Rice University
thesis.degree.level Doctoral
thesis.degree.name Doctor of Philosophy
dc.identifier.citation Dews, Ian Charles. "Characterization of transmembrane domain interactions by the syndecan family of integral membrane proteins." (2008) Diss., Rice University. https://hdl.handle.net/1911/22270.


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