Structural and biophysical characterization of the myocilin olfactomedin domain

Myocilin;Olfactomedin;Protein crystallography

Donegan, Rebecca Kristen ; Williams, Loren D. Chemistry and Biochemistry Schmidt-Krey, Ingeborg Zhu, Cheng Oyelere, Adegboyega ; Williams, Loren D.

University:Georgia Institute of Technology

Department:Chemistry and Biochemistry

关键词: Myocilin;    Olfactomedin;    Protein crystallography;   

Others  :  https://smartech.gatech.edu/bitstream/1853/53872/1/DONEGAN-DISSERTATION-2015.pdf

美国|英语

来源: SMARTech Repository

【 摘 要 】

The myocilin olfactomedin domain (myoc-OLF) is linked to inherited forms of open angle glaucoma.Mutant myocilin accumulates within the endoplasmic reticulum of human trabecular meshwork cells leading to cell death and the build up of intraocular pressure, a common risk factor for glaucoma. In this work, a novel high affinity calcium-binding site buried within myoc-OLF was characterized.Additionally amyloidogenic peptide stretches within myoc-OLF that may be responsible for mutant myocilin aggregation were determined. Additionally the crystal structure of myoc-OLF was solved providing the first crystal structure of an olfactomedin domain protein. Insights from the structure into the relationship between disease causing mutations and myoc-OLF misfolding and the currently unknown function of myoc-OLF as explored by structural based prediction of ligand binding are also discussed.