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Structural studies of full-length thioesterase superfamily member 1


EMSL Project ID
51308

Abstract

Thioesterase superfamily member 1 (Them1) suppresses thermogenesis in brown adipose tissue through hydrolyzing acyl-CoA destined for beta-oxidation. Ablation of Them1 in mice increases energy expenditure and prevents diet-induced obesity and other metabolic disorders. Them1 is a multi-domain enzyme that is allosterically regulated by multiple metabolites. ATP enhances while ADP inhibits Them1 activity, but mechanisms by which they regulate activity remains unknown. Furthermore, Them1 contains a lipid-binding START domain that serves as a lipid sensor to regulate Them1 activity. To elucidate how metabolites regulate Them1 activity, we aim to solve the cryo-EM structure of full-length Them1. We have already screened this sample to assess the best ice conditions and particle distribution. Data collection is currently stalled on our in-house Arctica as it is undergoing a detector upgrade and will be unavailable for several months. Therefore, we request data collection time on either the Arctica or Krios with a K3 detector.

Project Details

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

Team

Principal Investigator

Eric Ortlund
Institution
Emory University

Co-Investigator(s)

Anamika Patel
Institution
Emory University

Team Members

Matthew Tillman
Institution
Emory University