Journal article
Using a ubiquitin ligase as an unfolded protein sensor
Biochemical and biophysical research communications, Vol.418(1), pp.44-48
02/03/2012
DOI: 10.1016/j.bbrc.2011.12.109
PMID: 22227190
Abstract
► FBXO2 is a lectin-like ubiquitin ligase. ► FBXO2 binds only the exposed glycan core of glycoproteins. ► This core is only exposed on misfolded or denatured glycoproteins. ► Hence, FBXO2 can be used to develop an unfolded glycoprotein assay.
A significant fraction of all proteins are misfolded and must be degraded. The ubiquitin–proteasome pathway provides an essential protein quality control function necessary for normal cellular homeostasis. Substrate specificity is mediated by proteins called ubiquitin ligases. In the endoplasmic reticulum (ER) a specialized pathway, the endoplasmic reticulum associated degradation (ERAD) pathway provides means to eliminate misfolded proteins from the ER. One marker used by the ER to identify misfolded glycoproteins is the presence of a high-mannose (Man5-8GlcNAc2) glycan. Recently, FBXO2 was shown to bind high mannose glycans and participate in ERAD. Using glycan arrays, immobilized glycoprotein pulldowns, and glycan competition assays we demonstrate that FBXO2 preferentially binds unfolded glycoproteins. Using recombinant, bacterially expressed GST-FBXO2 as an unfolded protein sensor we demonstrate it can be used to monitor increases in misfolded glycoproteins after physiological or pharmaceutical stressors.
Details
- Title: Subtitle
- Using a ubiquitin ligase as an unfolded protein sensor
- Creators
- Adam Mallinger - Kansas City University of Medicine and Biosciences, Kansas City, MO 64106, United StatesHsiang M Wen - Department of Internal Medicine, University of Iowa Hospitals and Clinics, Iowa City, IA 52242, United StatesGeoffrey M Dankle - Department of Internal Medicine, University of Iowa Hospitals and Clinics, Iowa City, IA 52242, United StatesKevin A Glenn - Department of Internal Medicine, University of Iowa Hospitals and Clinics, Iowa City, IA 52242, United States
- Resource Type
- Journal article
- Publication Details
- Biochemical and biophysical research communications, Vol.418(1), pp.44-48
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.bbrc.2011.12.109
- PMID
- 22227190
- ISSN
- 0006-291X
- eISSN
- 1090-2104
- Language
- English
- Date published
- 02/03/2012
- Academic Unit
- Psychiatry; General Internal Medicine; Internal Medicine
- Record Identifier
- 9984094761402771
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