TY  - GEN
AB  - The dim-light photoreceptor rhodopsin has been a structural model for G protein-coupled receptors (GPCRs) for decades, so much so that the largest class of GPCRs is commonly called “rhodopsin-like.” However, the visual receptor has several unique  characteristics that differentiate it from other members of the superfamily. Most notably, rather than interacting through a diffusible ligand, the receptor covalently binds its light-sensitive inverse agonist, 11-cis retinal (11CR), which locks the complex in an “off”  state. Activation occurs when the 11CR-rhodopsin complex absorbs light, and isomerizes the ligand into the agonist all-trans retinal (ATR). After activation, the ATR is exchanged for a fresh 11CR in order to reset the protein for further light detection. Therefore, despite the covalent nature of the retinal-rhodopsin interaction, the ligand must be capable of entering and exiting the receptor. So it may come as a surprise that, although rhodopsin was the first solved GPCR crystal structure, how the retinals bind and dissociate from the protein remains unanswered. This dissertation attempts to address this question.
AD  - Oregon Health and Science University
AU  - Schafer, Christopher
DA  - 2016-06-01
DO  - 10.6083/M4P849ZK
DO  - DOI
ED  - Farrens, David
ED  - Chapman, Michael
ED  - Shinde, Ujwal
ED  - Valiyaveetil, Francis
ED  - Whorton, Matthew
ED  - Mitchell, Drake
ED  - Advisor
ED  - Mentor
ED  - Committee chair
ED  - Committee member
ED  - Committee member
ED  - Committee member
ED  - Committee member
ID  - 2988
KW  - Ligands
KW  - Retinaldehyde
KW  - Drug Inverse Agonism
KW  - Models, Structural
KW  - Receptors, G-Protein-Coupled
KW  - Rhodopsin
L1  - https://digitalcollections.ohsu.edu/record/2988/files/3787_etd.pdf
L2  - https://digitalcollections.ohsu.edu/record/2988/files/3787_etd.pdf
L4  - https://digitalcollections.ohsu.edu/record/2988/files/3787_etd.pdf
LK  - https://digitalcollections.ohsu.edu/record/2988/files/3787_etd.pdf
N2  - The dim-light photoreceptor rhodopsin has been a structural model for G protein-coupled receptors (GPCRs) for decades, so much so that the largest class of GPCRs is commonly called “rhodopsin-like.” However, the visual receptor has several unique  characteristics that differentiate it from other members of the superfamily. Most notably, rather than interacting through a diffusible ligand, the receptor covalently binds its light-sensitive inverse agonist, 11-cis retinal (11CR), which locks the complex in an “off”  state. Activation occurs when the 11CR-rhodopsin complex absorbs light, and isomerizes the ligand into the agonist all-trans retinal (ATR). After activation, the ATR is exchanged for a fresh 11CR in order to reset the protein for further light detection. Therefore, despite the covalent nature of the retinal-rhodopsin interaction, the ligand must be capable of entering and exiting the receptor. So it may come as a surprise that, although rhodopsin was the first solved GPCR crystal structure, how the retinals bind and dissociate from the protein remains unanswered. This dissertation attempts to address this question.
PY  - 2016-06-01
T1  - Role of receptor conformation in retinal interactions with the visual GPCR rhodopsin
TI  - Role of receptor conformation in retinal interactions with the visual GPCR rhodopsin
UR  - https://digitalcollections.ohsu.edu/record/2988/files/3787_etd.pdf
Y1  - 2016-06-01
ER  -