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Structure and function of misfolded rhodopsin protein in Retinitis pigmentosa.

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Call No.	RE661.R45 S76 2004
Author	Stojanovic, Aleksandar, 1977-
Title	Structure and function of misfolded rhodopsin protein in Retinitis pigmentosa.
Date	2004
Abstract	Retinitis Pigmentosa is an inherited retinal degenerative disorder, initiated by point mutations on the rhodopsin gene. This thesis set forth to understand the mechanism of this pathogenesis, as well as to further improve our understanding of rhodopsin and G protein-coupled receptor (GPCR) structure and function. Additionally, studies on a second GPCR, the human prostacyclin (PGI 2 ) receptor, would further support these studies. (I) Using site-directed mutagenesis and molecular modeling of the rhodopsin crystal structure, this thesis identifies a novel transmembrane interhelical interaction, a zinc coordination site, in rhodopsin that is required for the structure and function of rhodopsin. These studies provide the structural requirements for the formation and attempt to understand the role and function of this zinc coordination site. (II) Furthermore, using similar approaches, these studies contribute to the understanding of the structural basis of Retinitis Pigmentosa and aid in the development of novel therapeutics for the treatment of this debilitating disease. This thesis elucidates the mechanism through which a cluster of Retinitis Pigmentosa mutations, near the β-ionone ring of 11- cis -retinal, disturb the structure and function of rhodopsin. Two separate mutations within this cluster were identified as interfering with the formation of the transmembrane zinc coordination site, resulting in the deleterious effects observed with the pathogenesis of Retinitis Pigmentosa.
Description	xxv, 248 leaves : ill. (some col.) 28 cm.
Format	application/pdf
Advisor	Christopher Lowrey.
Subject	Retinitis pigmentosa -- Pathogenesis. Retinitis pigmentosa -- Genetic aspects. Rhodopsin. G proteins -- Receptors. Prostacyclin -- Receptors.
College	Dartmouth Medical School -- Department of Pharmacology and Toxicology.
Issuing Body	Dartmouth Dissertations are made available through the Dartmouth Digital Library.
Degree	Thesis (Ph.D.)--Dartmouth College.
Copyright	All rights reserved. No part of this book may be reproduced in any form by any electronic or mechanical means without permission in writing from the author.
DOI	http://dx.doi.org/10.1349/ddlp.47

Title	Page 1
Format	application/pdf
Issuing Body	Dartmouth Dissertations are made available through the Dartmouth Digital Library.
Degree	Thesis (Ph.D.)--Dartmouth College.
Full Text	Structure and Function of Misfolded Rhodopsin Protein in Retinitis Pigmentosa A Thesis Submitted to the Faculty in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Pharmacology and Toxicology by Aleksandar Stojanovic DARTMOUTH COLLEGE Hanover, New Hampshire 5-26-04 ______________________________ Author Thesis Committee ______________________________ (Committee Chairperson) Christopher Lowrey, M.D. ______________________________ (Thesis Advisor) John Hwa, M.D., Ph.D. ______________________________ Amy C. Anderson, Ph.D. ______________________________ Patrick Dolph, Ph.D. ______________________ Carol Folt, Ph.D. Dean of Graduate Studies

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