dc.creator | Dattilo, Brian Matthew | |
dc.date.accessioned | 2020-08-22T17:00:56Z | |
dc.date.available | 2008-05-30 | |
dc.date.issued | 2007-05-30 | |
dc.identifier.uri | https://etd.library.vanderbilt.edu/etd-05302007-114804 | |
dc.identifier.uri | http://hdl.handle.net/1803/12425 | |
dc.description.abstract | The Receptor for Advanced Glycation End Products (RAGE) contains a single transmembrane helix, a small cytosolic domain, and an extracellular region (sRAGE) composed of three Ig-like domains (V, C1, C2). RAGE has been implicated in complications arising from diabetes and chronic inflammation and is widely thought to be a therapeutic target. In this dissertation, production of purified sRAGE and the five single and tandem domain constructs enabled biophysical and structural characterization. The results, including an x-ray crystal structure of VC1, show that the V and C1 domains form an integrated structural unit. In contrast, C2 is attached to VC1 by a flexible linker and is fully independent. Studies of the interaction with a known RAGE ligand, Ca2+-S100B, revealed a major contribution from the V domain but clearly defined contributions to binding from the C1 domain. The implications of these results are discussed with respect to models for sRAGE quaternary structure and RAGE signaling. | |
dc.format.mimetype | application/pdf | |
dc.subject | Structural Biology | |
dc.subject | RAGE | |
dc.subject | Receptor for Advanced Glycation End Products | |
dc.subject | Soluble RAGE | |
dc.subject | Receptor Signaling | |
dc.subject | S100 Proteins | |
dc.subject | Ligands (Biochemistry) | |
dc.title | Structural characterization of the receptor for advanced glycation end products reveals a two domain modular architecture | |
dc.type | dissertation | |
dc.contributor.committeeMember | Charles R. Sanders, II | |
dc.contributor.committeeMember | Martin Egli | |
dc.contributor.committeeMember | Billy G. Hudson | |
dc.type.material | text | |
thesis.degree.name | PHD | |
thesis.degree.level | dissertation | |
thesis.degree.discipline | Biochemistry | |
thesis.degree.grantor | Vanderbilt University | |
local.embargo.terms | 2008-05-30 | |
local.embargo.lift | 2008-05-30 | |
dc.contributor.committeeChair | Walter J. Chazin | |