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Cryo-EM structural analysis of Glucose-6-phosphatase catalytic subunit, G6PC1


EMSL Project ID
51576

Abstract

The catalytic subunit of glucose-6-phosphatase, G6PC1, functions as a gatekeeper of glucose production in the liver by catalyzing the hydrolysis of glucose-6-phosphate. Dysregulation of G6PC1 gene expression contributes to elevated hepatic glucose production associated with diabetes, and more than 100 debilitating mutations lead to glycogen storage disease type 1a. There are no high-resolution structures of G6PC1, which would support a more complete understanding of its mechanistic biology. This proposal aims to obtain the first atomic-scale models of G6PC1 by collecting cryo-EM datasets on the PNCC Krios. We request a total of 72 hrs of microscope time. The ultimate goal of these efforts is to define the molecular architecture of G6PC1 in order to identify the relative position of disease-causing mutations and protein-protein interaction motifs. The results of this work will set the stage for a description of the structural basis of G6PC1 activity and the relationship to disease-associated mutations.

Project Details

Start Date
2020-09-15
End Date
2021-03-17
Status
Closed

Team

Principal Investigator

Hassane Mchaourab
Institution
Vanderbilt University

Co-Investigator(s)

Erkan Karakas
Institution
Vanderbilt University

Team Members

Derek Claxton
Institution
Vanderbilt University

Brinda Selvaraj
Institution
Vanderbilt University

Irina El Khoury
Institution
Environmental Molecular Sciences Laboratory